Prevention of Endothelial Dysfunction and Cardiovascular Disease by n-3 Fatty Acids-Inhibiting Action on Oxidative Stress and Inflammation

Kazuo       Yamagata
doi:10.2174/1381612826666200403121952
Abstract

Background: Prospective cohort studies and randomized controlled trials have shown the protective effect of n-3 fatty acids against cardiovascular disease (CVD). The effect of n-3 fatty acids on vascular endothelial cells indicates their possible role in CVD prevention.
Objective: Here, we describe the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on endothelial dysfunction-caused by inflammation and oxidative stress-and their role in the development of CVD.
Methods: We reviewed epidemiological studies done on n-3 fatty acids in CVD. The effect of DHA and EPA on vascular endothelial cells was examined with regard to changes in various markers, such as arteriosclerosis, inflammation, and oxidative stress, using cell and animal models.
Results: Epidemiological studies revealed that dietary intake of EPA and DHA was associated with a reduced risk of various CVDs. EPA and DHA inhibited various events involved in arteriosclerosis development by preventing oxidative stress and inflammation associated with endothelial cell damage. In particular, EPA and DHA prevented endothelial cell dysfunction mediated by inflammatory responses and oxidative stress induced by events related to CVD. DHA and EPA also increased eNOS activity and induced nitric oxide production.
Conclusion: The effects of DHA and EPA on vascular endothelial cell damage and dysfunction may involve the induction of nitric oxide, in addition to antioxidant and anti-inflammatory effects. n-3 fatty acids inhibit endothelial dysfunction and prevent arteriosclerosis. Therefore, the intake of n-3 fatty acids may prevent CVDs, like myocardial infarction and stroke.
Keywords: DHA, EPA, endothelial cells, reactive oxygen species, inflammation, stroke, myocardial infarction.
« Previous Next »
[1] 
GBD 2015 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet  2016; 388(10053): 1603-58.
[http://dx.doi.org/10.1016/S0140-6736(16)31460-X] [PMID:  27733283] 
[2] 
Alqahtani F, Aljohani S, Tarabishy A, Busu T, Adcock A, Alkhouli M. Incidence and outcomes of myocardial infarction in patients admitted with acute ischemic stroke. Stroke  2017; 48(11): 2931-8.
[http://dx.doi.org/10.1161/STROKEAHA.117.018408] [PMID:  29018137] 
[3] 
Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature  2011; 473(7347): 317-25.
[http://dx.doi.org/10.1038/nature10146] [PMID:  21593864] 
[4] 
Pedersen LR, Frestad D, Michelsen MM, et al. Risk factors for myocardial infarction in women and men: a review of the current literature. Curr Pharm Des  2016; 22(25): 3835-52.
[http://dx.doi.org/10.2174/1381612822666160309115318] [PMID:  26956230] 
[5] 
Bousser MG. Stroke prevention: an update. Front Med  2012; 6(1): 22-34.
[http://dx.doi.org/10.1007/s11684-012-0178-6] [PMID:  22460445] 
[6] 
Bradley JM, Organ CL, Lefer DJ. Garlic-derived organic polysulfides and myocardial protection. J Nutr  2016; 146(2): 403S-9S.
[http://dx.doi.org/10.3945/jn.114.208066] [PMID:  26764335] 
[7] 
Moraes-Silva IC, Rodrigues B, Coelho-Junior HJ, Feriani DJ, Irigoyen MC. Myocardial infarction and exercise training: evidence from basic science. Adv Exp Med Biol  2017; 999: 139-53.
[http://dx.doi.org/10.1007/978-981-10-4307-9_9] [PMID:  29022262] 
[8] 
Tektonidis TG, Åkesson A, Gigante B, Wolk A, Larsson SC. A mediterranean diet and risk of myocardial infarction, heart failure and stroke: a population-based cohort study. Atherosclerosis  2015; 243(1): 93-8.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.08.039] [PMID:  26363438] 
[9] 
Gimbrone MA Jr, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res  2016; 118(4): 620-36.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306301] [PMID:  26892962] 
[10] 
Smiljic S. The clinical significance of endocardial endothelial dysfunction. Medicina (Kaunas)  2017; 53(5): 295-302.
[http://dx.doi.org/10.1016/j.medici.2017.08.003] [PMID:  29074341] 
[11] 
Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol  2003; 23(2): 168-75.
[http://dx.doi.org/10.1161/01.ATV.0000051384.43104.FC] [PMID:  12588755] 
[12] 
Vanhoutte PM, Shimokawa H, Feletou M, Tang EH. Endothelial dysfunction and vascular disease - a 30th anniversary update. Acta Physiol (Oxf)  2017; 219(1): 22-96.
[http://dx.doi.org/10.1111/apha.12646] [PMID:  26706498] 
[13] 
Boulanger CM. Endothelium. Arterioscler Thromb Vasc Biol  2016; 36(4): e26-31.
[http://dx.doi.org/10.1161/ATVBAHA.116.306940] [PMID:  27010027] 
[14] 
Godo S, Shimokawa H. Endothelial functions. Arterioscler Thromb Vasc Biol  2017; 37(9): e108-14.
[http://dx.doi.org/10.1161/ATVBAHA.117.309813] [PMID:  28835487] 
[15] 
Bang HO, Dyerberg J, Hjøorne N. The composition of food consumed by Greenland Eskimos. Acta Med Scand  1976; 200(1-2): 69-73.
[http://dx.doi.org/10.1111/j.0954-6820.1976.tb08198.x] [PMID:  961471] 
[16] 
Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet  1978; 2(8081): 117-9.
[http://dx.doi.org/10.1016/S0140-6736(78)91505-2] [PMID:  78322] 
[17] 
Bowen KJ, Harris WS, Kris-Etherton PM. Omega-3 fatty acids and cardiovascular disease: are there benefits? Curr Treat Options Cardiovasc Med  2016; 18(11): 69.
[http://dx.doi.org/10.1007/s11936-016-0487-1] [PMID:  27747477] 
[18] 
Balk EM, Adams GP, Langberg V, et al. Omega-3 fatty acids and cardiovascular disease: an updated systematic review. Evid Rep Technol Assess (Full Rep)  2016; (223): 1-1252.
[http://dx.doi.org/10.23970/AHRQEPCERTA223] [PMID:  30307737] 
[19] 
Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA  2012; 308(10): 1024-33.
[http://dx.doi.org/10.1001/2012.jama.11374] [PMID:  22968891] 
[20] 
Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol  2011; 58(20): 2047-67.
[http://dx.doi.org/10.1016/j.jacc.2011.06.063] [PMID:  22051327] 
[21] 
Saber H, Yakoob MY, Shi P, et al. Omega-3 fatty acids and incident ischemic stroke and its atherothrombotic and cardioembolic subtypes in 3 US cohorts. Stroke  2017; 48(10): 2678-85.
[http://dx.doi.org/10.1161/STROKEAHA.117.018235] [PMID:  28830976] 
[22] 
Yaemsiri S, Sen S, Tinker LF, et al. Serum fatty acids and incidence of ischemic stroke among postmenopausal women. Stroke  2013; 44(10): 2710-7.
[http://dx.doi.org/10.1161/STROKEAHA.111.000834] [PMID:  23899914] 
[23] 
Mozaffarian D, Wu JH. (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr  2012; 142(3): 614S-25.
[http://dx.doi.org/10.3945/jn.111.149633] [PMID:  22279134] 
[24] 
Fleming JA, Kris-Etherton PM. The evidence for α-linolenic acid and cardiovascular disease benefits: Comparisons with eicosapentaenoic acid and docosahexaenoic acid. Adv Nutr  2014; 5(6): 863S-76S.
[http://dx.doi.org/10.3945/an.114.005850] [PMID:  25398754] 
[25] 
Saini RK, Keum YS. Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance - A review. Life Sci  2018; 203: 255-67.
[http://dx.doi.org/10.1016/j.lfs.2018.04.049] [PMID:  29715470] 
[26] 
Baum SJ, Kris-Etherton PM, Willett WC, et al. Fatty acids in cardiovascular health and disease: a comprehensive update. J Clin Lipidol  2012; 6(3): 216-34.
[http://dx.doi.org/10.1016/j.jacl.2012.04.077] [PMID:  22658146] 
[27] 
Willett WC. Dietary fats and coronary heart disease. J Intern Med  2012; 272(1): 13-24.
[http://dx.doi.org/10.1111/j.1365-2796.2012.02553.x] [PMID:  22583051] 
[28] 
de Oliveira Otto MC, Wu JH, Baylin A, et al. Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the multi-ethnic study of atherosclerosis. J Am Heart Assoc  2013; 2(6)e000506
[http://dx.doi.org/10.1161/JAHA.113.000506] [PMID:  24351702] 
[29] 
Cottin SC, Sanders TA, Hall WL. The differential effects of EPA and DHA on cardiovascular risk factors. Proc Nutr Soc  2011; 70(2): 215-31.
[http://dx.doi.org/10.1017/S0029665111000061] [PMID:  21349231] 
[30] 
Stebbins CL, Stice JP, Hart CM, Mbai FN, Knowlton AA. Effects of dietary decosahexaenoic acid (DHA) on eNOS in human coronary artery endothelial cells. J Cardiovasc Pharmacol Ther  2008; 13(4): 261-8.
[http://dx.doi.org/10.1177/1074248408322470] [PMID:  18682551] 
[31] 
Wang TM, Chen CJ, Lee TS, et al. Docosahexaenoic acid attenuates VCAM-1 expression and NF-κB activation in TNF-α-treated human aortic endothelial cells. J Nutr Biochem  2011; 22(2): 187-94.
[http://dx.doi.org/10.1016/j.jnutbio.2010.01.007] [PMID:  20573493] 
[32] 
Ohnishi H, Saito Y. Eicosapentaenoic acid (EPA) reduces cardiovascular events: relationship with the EPA/arachidonic acid ratio. J Atheroscler Thromb  2013; 20(12): 861-77.
[http://dx.doi.org/10.5551/jat.18002] [PMID:  24047614] 
[33] 
Hagen TP, Anthun KS, Reikvam A. Acute myocardial infarctions in Norway 1991 - 2007. Tidsskr Nor Laegeforen  2010; 130(8): 820-4.
[http://dx.doi.org/10.4045/tidsskr.09.0533] [PMID:  20418926] 
[34] 
Mozaffarian D, Benjamin EJ, Go AS, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation  2015; 131(4): e29-322.
[http://dx.doi.org/10.1161/CIR.0000000000000152] [PMID:  25520374] 
[35] 
Jensen HA, Mehta JL. Endothelial cell dysfunction as a novel therapeutic target in atherosclerosis. Expert Rev Cardiovasc Ther  2016; 14(9): 1021-33.
[http://dx.doi.org/10.1080/14779072.2016.1207527] [PMID:  27362558] 
[36] 
Widlansky ME, Gokce N, Keaney JF Jr, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol  2003; 42(7): 1149-60.
[http://dx.doi.org/10.1016/S0735-1097(03)00994-X] [PMID:  14522472] 
[37] 
Le Brocq M, Leslie SJ, Milliken P, Megson IL. Endothelial dysfunction: from molecular mechanisms to measurement, clinical implications, and therapeutic opportunities. Antioxid Redox Signal  2008; 10(9): 1631-74.
[http://dx.doi.org/10.1089/ars.2007.2013] [PMID:  18598143] 
[38] 
Liu X, Wu J, Zhu C, et al. Endothelial S1pr1 regulates pressure overload-induced cardiac remodelling through AKT-eNOS pathway. J Cell Mol Med 2019. Epub ahead of print 
[PMID:  31854513] 
[39] 
Patel D, Alhawaj R, Kelly MR, et al. Potential role of mitochondrial superoxide decreasing ferrochelatase and heme in coronary artery soluble guanylate cyclase depletion by angiotensin II. Am J Physiol Heart Circ Physiol  2016; 310(11): H1439-47.
[http://dx.doi.org/10.1152/ajpheart.00859.2015] [PMID:  27037373] 
[40] 
Li M, Tanaka Y, Alioua A, et al. Thromboxane A2 receptor and MaxiK-channel intimate interaction supports channel transinhibition independent of G-protein activation. Proc Natl Acad Sci USA  2010; 107(44): 19096-101.
[http://dx.doi.org/10.1073/pnas.1002685107] [PMID:  20959415] 
[41] 
Landmesser U, Drexler H. The clinical significance of endothelial dysfunction. Curr Opin Cardiol  2005; 20(6): 547-51.
[http://dx.doi.org/10.1097/01.hco.0000179821.11071.79] [PMID:  16234629] 
[42] 
Vanhoutte PM. Endothelial dysfunction: the first step toward coronary arteriosclerosis. Circ J  2009; 73(4): 595-601.
[http://dx.doi.org/10.1253/circj.CJ-08-1169] [PMID:  19225203] 
[43] 
Landmesser U, Drexler H. Endothelial function and hypertension. Curr Opin Cardiol  2007; 22(4): 316-20.
[http://dx.doi.org/10.1097/HCO.0b013e3281ca710d] [PMID:  17556884] 
[44] 
Kawashima S, Yokoyama M. Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol  2004; 24(6): 998-1005.
[http://dx.doi.org/10.1161/01.ATV.0000125114.88079.96] [PMID:  15001455] 
[45] 
Li H, Horke S, Förstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis  2014; 237(1): 208-19.
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.09.001] [PMID:  25244505] 
[46] 
Roquer J, Segura T, Serena J, Castillo J. Endothelial dysfunction, vascular disease and stroke: the ARTICO study. Cerebrovasc Dis  2009; 27(Suppl. 1): 25-37.
[http://dx.doi.org/10.1159/000200439] [PMID:  19342831] 
[47] 
Zhao Y, Vanhoutte PM, Leung SW. Vascular nitric oxide: Beyond eNOS. J Pharmacol Sci  2015; 129(2): 83-94.
[http://dx.doi.org/10.1016/j.jphs.2015.09.002] [PMID:  26499181] 
[48] 
Pierini D, Bryan NS. Nitric oxide availability as a marker of oxidative stress. Methods Mol Biol  2015; 1208: 63-71.
[http://dx.doi.org/10.1007/978-1-4939-1441-8_5] [PMID:  25323499] 
[49] 
Incalza MA, D’Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol  2018; 100: 1-19.
[http://dx.doi.org/10.1016/j.vph.2017.05.005] [PMID:  28579545] 
[50] 
Dikalov SI, Nazarewicz RR, Bikineyeva A, et al. Nox2-induced production of mitochondrial superoxide in angiotensin II-mediated endothelial oxidative stress and hypertension. Antioxid Redox Signal  2014; 20(2): 281-94.
[http://dx.doi.org/10.1089/ars.2012.4918] [PMID:  24053613] 
[51] 
Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res  2017; 120(4): 713-35.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309326] [PMID:  28209797] 
[52] 
Huynh DTN, Heo KS. Therapeutic targets for endothelial dysfunction in vascular diseases. Arch Pharm Res  2019; 42(10): 848-61.
[http://dx.doi.org/10.1007/s12272-019-01180-7] [PMID:  31420777] 
[53] 
Gielis JF, Lin JY, Wingler K, Van Schil PE, Schmidt HH, Moens AL. Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders. Free Radic Biol Med  2011; 50(7): 765-76.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.12.018] [PMID:  21172428] 
[54] 
Osterbur K, Yu DH, DeClue AE. Interleukin-1β, tumour necrosis factor-α and lipopolysaccharide induce C-type natriuretic peptide from canine aortic endothelial cells. Res Vet Sci  2013; 94(3): 478-83.
[http://dx.doi.org/10.1016/j.rvsc.2012.10.002] [PMID:  23141169] 
[55] 
Ng CT, Fong LY, Sulaiman MR, et al. Interferon-gamma increases endothelial permeability by causing activation of p38 map kinase and actin cytoskeleton alteration. J Interferon Cytokine Res  2015; 35(7): 513-22.
[http://dx.doi.org/10.1089/jir.2014.0188] [PMID:  25830506] 
[56] 
Fairaq A, Goc A, Artham S, Sabbineni H, Somanath PR. TNFα induces inflammatory stress response in microvascular endothelial cells via Akt- and P38 MAP kinase-mediated thrombospondin-1 expression. Mol Cell Biochem  2015; 406(1-2): 227-36.
[http://dx.doi.org/10.1007/s11010-015-2440-0] [PMID:  25963668] 
[57] 
Zhang Y, Yang X, Bian F, et al. TNF-α promotes early atherosclerosis by increasing transcytosis of LDL across endothelial cells: crosstalk between NF-κB and PPAR-γ. J Mol Cell Cardiol  2014; 72: 85-94.
[http://dx.doi.org/10.1016/j.yjmcc.2014.02.012] [PMID:  24594319] 
[58] 
Brand K, Page S, Rogler G, et al. Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Invest  1996; 97(7): 1715-22.
[http://dx.doi.org/10.1172/JCI118598] [PMID:  8601637] 
[59] 
Morigi M, Angioletti S, Imberti B, et al. Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion. J Clin Invest  1998; 101(9): 1905-15.
[http://dx.doi.org/10.1172/JCI656] [PMID:  9576755] 
[60] 
Rollins BJ, Yoshimura T, Leonard EJ, Pober JS. Cytokine activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am J Pathol  1990; 136(6): 1229-33.
[PMID:  2113354] 
[61] 
Gimbrone MA Jr, Obin MS, Brock AF, et al. Endothelial interleukin- 8: a novel inhibitor of leukocyte-endothelial interactions. Science  1989; 246(4937): 1601-3.
[http://dx.doi.org/10.1126/science.2688092] [PMID:  2688092] 
[62] 
Radecke CE, Warrick AE, Singh GD, Rogers JH, Simon SI, Armstrong EJ. Coronary artery endothelial cells and microparticles increase expression of VCAM-1 in myocardial infarction. Thromb Haemost  2015; 113(3): 605-16.
[http://dx.doi.org/10.1160/TH14-02-0151] [PMID:  25413339] 
[63] 
Collins T, Cybulsky MI. NF-kappaB: pivotal mediator or innocent bystander in atherogenesis? J Clin Invest  2001; 107(3): 255-64.
[http://dx.doi.org/10.1172/JCI10373] [PMID:  11160146] 
[64] 
Ihling C, Szombathy T, Bohrmann B, Brockhaus M, Schaefer HE, Loeffler BM. Coexpression of endothelin-converting enzyme-1 and endothelin-1 in different stages of human atherosclerosis. Circulation  2001; 104(8): 864-9.
[http://dx.doi.org/10.1161/hc3301.094742] [PMID:  11514370] 
[65] 
Adamopoulos C, Piperi C, Gargalionis AN, et al. Advanced glycation end products upregulate lysyl oxidase and endothelin-1 in human aortic endothelial cells via parallel activation of ERK1/2-NF- κB and JNK-AP-1 signaling pathways. Cell Mol Life Sci  2016; 73(8): 1685-98.
[http://dx.doi.org/10.1007/s00018-015-2091-z] [PMID:  26646068] 
[66] 
Zhang X, Wu M, Jiang H, et al. Angiotensin II upregulates endothelial lipase expression via the NF-kappa B and MAPK signaling pathways. PLoS One  2014; 9(9), e107634.
[http://dx.doi.org/10.1371/journal.pone.0107634] [PMID:  25250890] 
[67] 
Stangl V, Günther C, Jarrin A, et al. Homocysteine inhibits TNF alpha- induced endothelial adhesion molecule expression and monocyte adhesion via nuclear factor-kappaB dependent pathway. Biochem Biophys Res Commun  2001; 280(4): 1093-100.
[http://dx.doi.org/10.1006/bbrc.2000.4207] [PMID:  11162639] 
[68] 
Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol  2009; 1(6), a001651.
[http://dx.doi.org/10.1101/cshperspect.a001651] [PMID:  20457564] 
[69] 
Sies H, Berndt C, Jones DP. Oxidative Stress. Annu Rev Biochem  2017; 86: 715-48.
[http://dx.doi.org/10.1146/annurev-biochem-061516-045037] [PMID:  28441057] 
[70] 
Yu XH, Zheng XL, Tang CK. Nuclear factor-κB activation as a pathological mechanism of lipid metabolism and atherosclerosis. Adv Clin Chem  2015; 70: 1-30.
[http://dx.doi.org/10.1016/bs.acc.2015.03.004] [PMID:  26231484] 
[71] 
Lubrano V, Balzan S. Enzymatic antioxidant system in vascular inflammation and coronary artery disease. World J Exp Med  2015; 5(4): 218-24.
[http://dx.doi.org/10.5493/wjem.v5.i4.218] [PMID:  26618108] 
[72] 
Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal  2011; 15(6): 1583-606.
[http://dx.doi.org/10.1089/ars.2011.3999] [PMID:  21473702] 
[73] 
Abdukeyum GG, Owen AJ, Larkin TA, McLennan PL. Up regulation of mitochondrial antioxidant superoxide dismutase underpins persistent cardiac nutritional-preconditioning by long chain n-3 polyunsaturated fatty acids in the rat. J Clin Med  2016; 5(3): 5.
[http://dx.doi.org/10.3390/jcm5030032] [PMID:  26959067] 
[74] 
Lin SJ, Shyue SK, Hung YY, et al. Superoxide dismutase inhibits the expression of vascular cell adhesion molecule-1 and intracellular cell adhesion molecule-1 induced by tumor necrosis factor alpha in human endothelial cells through the JNK/p38 pathways. Arterioscler Thromb Vasc Biol  2005; 25(2): 334-40.
[http://dx.doi.org/10.1161/01.ATV.0000152114.00114.d8] [PMID:  15576639] 
[75] 
Nelson SK, Bose SK, McCord JM. The toxicity of high-dose superoxide dismutase suggests that superoxide can both initiate and terminate lipid peroxidation in the reperfused heart. Free Radic Biol Med  1994; 16(2): 195-200.
[http://dx.doi.org/10.1016/0891-5849(94)90143-0] [PMID:  8005514] 
[76] 
Ershova OA, Bairova TA, Kolesnikov SI, Kalyuzhnaya OV, Darenskaya MA, Kolesnikova LI. Oxidative stress and catalase gene. Bull Exp Biol Med  2016; 161(3): 400-3.
[http://dx.doi.org/10.1007/s10517-016-3424-0] [PMID:  27496033] 
[77] 
Yang H, Roberts LJ, Shi MJ, et al. Retardation of atherosclerosis by overexpression of catalase or both Cu/Zn-superoxide dismutase and catalase in mice lacking apolipoprotein E. Circ Res  2004; 95(11): 1075-81.
[http://dx.doi.org/10.1161/01.RES.0000149564.49410.0d] [PMID:  15528470] 
[78] 
Yang H, Zhou L, Wang Z, et al. Overexpression of antioxidant enzymes in ApoE-deficient mice suppresses benzo(a)pyrene accelerated atherosclerosis. Atherosclerosis  2009; 207(1): 51-8.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.03.052] [PMID:  19409565] 
[79] 
Lubos E, Loscalzo J, Handy DE. Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal  2011; 15(7): 1957-97.
[http://dx.doi.org/10.1089/ars.2010.3586] [PMID:  21087145] 
[80] 
Blankenberg S, Rupprecht HJ, Bickel C, et al. AtheroGene Investigators. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med  2003; 349(17): 1605-13.
[http://dx.doi.org/10.1056/NEJMoa030535] [PMID:  14573732] 
[81] 
Oelze M, Kröller-Schön S, Steven S, et al. Glutathione peroxidase- 1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging. Hypertension  2014; 63(2): 390-6.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01602] [PMID:  24296279] 
[82] 
Cheng F, Torzewski M, Degreif A, Rossmann H, Canisius A, Lackner KJ. Impact of glutathione peroxidase-1 deficiency on macrophage foam cell formation and proliferation: implications for atherogenesis. PLoS One  2013; 8(8)e72063
[http://dx.doi.org/10.1371/journal.pone.0072063] [PMID:  23991041] 
[83] 
Chew P, Yuen DY, Koh P, et al. Site-specific antiatherogenic effect of the antioxidant ebselen in the diabetic apolipoprotein E-deficient mouse. Arterioscler Thromb Vasc Biol  2009; 29(6): 823-30.
[http://dx.doi.org/10.1161/ATVBAHA.109.186619] [PMID:  19325139] 
[84] 
Guo Z, Ran Q, Roberts LJ II, et al. Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E deficient mice. Free Radic Biol Med  2008; 44(3): 343-52.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.09.009] [PMID:  18215741] 
[85] 
Bosch J, Gerstein HC, Dagenais GR, et al. ORIGIN Trial Investigators. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med  2012; 367(4): 309-18.
[http://dx.doi.org/10.1056/NEJMoa1203859] [PMID:  22686415] 
[86] 
Risk, Prevention Study Collaborative G ,. Roncaglioni MC, Tombesi M, Avanzini F, et al. n-3 fatty acids in patients with multiple cardiovascular
risk factors. N Engl J Med  2013; 368: 1800-8.
[87] 
Tavazzi L, Maggioni AP, Marchioli R, et al. Gissi-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double blind, placebo-controlled trial. Lancet  2008; 372(9645): 1223-30.
[http://dx.doi.org/10.1016/S0140-6736(08)61239-8] [PMID:  18757090] 
[88] 
Zheng J, Huang T, Yu Y, Hu X, Yang B, Li D. Fish consumption and CHD mortality: an updated meta-analysis of seventeen cohort studies. Public Health Nutr  2012; 15(4): 725-37.
[http://dx.doi.org/10.1017/S1368980011002254] [PMID:  21914258] 
[89] 
Maehre HK, Jensen IJ, Elvevoll EO, Eilertsen KE. ω-3 fatty acids and cardiovascular diseases: effects, mechanisms and dietary relevance. Int J Mol Sci  2015; 16(9): 22636-61.
[http://dx.doi.org/10.3390/ijms160922636] [PMID:  26393581] 
[90] 
Chowdhury R, Stevens S, Gorman D, et al. Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis. BMJ  2012; 345, e6698.
[http://dx.doi.org/10.1136/bmj.e6698] [PMID:  23112118] 
[91] 
Djoussé L, Akinkuolie AO, Wu JH, Ding EL, Gaziano JM. Fish consumption, omega-3 fatty acids and risk of heart failure: a meta analysis. Clin Nutr  2012; 31(6): 846-53.
[http://dx.doi.org/10.1016/j.clnu.2012.05.010] [PMID:  22682084] 
[92] 
Li YH, Zhou CH, Pei HJ, et al. Fish consumption and incidence of heart failure: a meta-analysis of prospective cohort studies. Chin Med J (Engl)  2013; 126(5): 942-8.
[PMID:  23489806] 
[93] 
Xun P, Qin B, Song Y, et al. Fish consumption and risk of stroke and its subtypes: accumulative evidence from a meta-analysis of prospective cohort studies. Eur J Clin Nutr  2012; 66(11): 1199-207.
[http://dx.doi.org/10.1038/ejcn.2012.133] [PMID:  23031847] 
[94] 
Leung Yinko SS, Stark KD, Thanassoulis G, Pilote L. Fish consumption and acute coronary syndrome: a meta-analysis. Am J Med   2014; 127: 848-57.,e2.
[http://dx.doi.org/10.1016/j.amjmed.2014.04.016] 
[95] 
Musa-Veloso K, Binns MA, Kocenas A, et al. Impact of low v. moderate intakes of long-chain n-3 fatty acids on risk of coronary heart disease. Br J Nutr  2011; 106(8): 1129-41.
[http://dx.doi.org/10.1017/S0007114511001644] [PMID:  21736820] 
[96] 
Delgado-Lista J, Perez-Martinez P, Lopez-Miranda J, Perez-Jimenez F. Long chain omega-3 fatty acids and cardiovascular disease: a systematic review. Br J Nutr  2012; 107(Suppl. 2): S201-13.
[http://dx.doi.org/10.1017/S0007114512001596] [PMID:  22591894] 
[97] 
Lee CH, Lee SD, Ou HC, Lai SC, Cheng YJ. Eicosapentaenoic acid protects against palmitic acid-induced endothelial dysfunction via activation of the AMPK/eNOS pathway. Int J Mol Sci  2014; 15(6): 10334-49.
[http://dx.doi.org/10.3390/ijms150610334] [PMID:  24918290] 
[98] 
Casula M, Soranna D, Catapano AL, Corrao G. Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials. Atheroscler Suppl  2013; 14(2): 243-51.
[http://dx.doi.org/10.1016/S1567-5688(13)70005-9] [PMID:  23958480] 
[99] 
Rizos EC, Ntzani EE, Elisaf MS. Omega-3 fatty acid supplementation and cardiovascular disease events--reply. JAMA  2013; 309(1): 29.
[http://dx.doi.org/10.1001/jama.2012.116657] [PMID:  23280212] 
[100] 
Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet  1999; 354(9177): 447-55.
[http://dx.doi.org/10.1016/S0140-6736(99)07072-5] [PMID:  10465168] 
[101] 
Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev  2018; 7: CD003177,
[PMID:  30019766] 
[102] 
Zheng T, Zhao J, Wang Y, et al. The limited effect of omega-3 polyunsaturated fatty acids on cardiovascular risk in patients with impaired glucose metabolism: a meta-analysis. Clin Biochem  2014; 47(6): 369-77.
[http://dx.doi.org/10.1016/j.clinbiochem.2013.11.025] [PMID:  24342751] 
[103] 
Wen YT, Dai JH, Gao Q. Effects of Omega-3 fatty acid on major cardiovascular events and mortality in patients with coronary heart disease: a meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis  2014; 24(5): 470-5.
[http://dx.doi.org/10.1016/j.numecd.2013.12.004] [PMID:  24472636] 
[104] 
Tajik B, Kurl S, Tuomainen TP, Savonen K, Virtanen JK. Associations of the serum long-chain n-3 PUFA and hair mercury with resting heart rate, peak heart rate during exercise and heart rate recovery after exercise in middle-aged men. Br J Nutr  2018; 119(1): 66-73.
[http://dx.doi.org/10.1017/S0007114517003191] [PMID:  29208059] 
[105] 
Jiang J, Li K, Wang F, et al. Effect of marine-derived n-3 polyunsaturated fatty acids on major eicosanoids: a systematic review and meta-analysis from 18 randomized controlled trials. PLoS One  2016; 11(1): e0147351,
[http://dx.doi.org/10.1371/journal.pone.0147351] [PMID:  26808318] 
[106] 
Watanabe Y, Tatsuno I. Omega-3 polyunsaturated fatty acids for cardiovascular diseases: present, past and future. Expert Rev Clin Pharmacol  2017; 10(8): 865-73.
[http://dx.doi.org/10.1080/17512433.2017.1333902] [PMID:  28531360] 
[107] 
Calder PC. Very long-chain n-3 fatty acids and human health: fact, fiction and the future. Proc Nutr Soc  2018; 77(1): 52-72.
[http://dx.doi.org/10.1017/S0029665117003950] [PMID:  29039280] 
[108] 
Sakamoto A, Saotome M, Iguchi K, Maekawa Y. Marine-derived omega-3 polyunsaturated fatty acids and heart failure: current understanding for basic to clinical relevance. Int J Mol Sci  2019; 20(16): 20.
[http://dx.doi.org/10.3390/ijms20164025] [PMID:  31426560] 
[109] 
Golzari MH, Javanbakht MH, Ghaedi E, Mohammadi H, Djalali M. Effect of Eicosapentaenoic acid (EPA) supplementation on cardiovascular markers in patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial. Diabetes Metab Syndr  2018; 12(3): 411-5.
[http://dx.doi.org/10.1016/j.dsx.2018.03.003] [PMID:  29588138] 
[110] 
Li Q, Zhang Q, Wang M, et al. Eicosapentaenoic acid modifies lipid composition in caveolae and induces translocation of endothelial nitric oxide synthase. Biochimie  2007; 89(1): 169-77.
[http://dx.doi.org/10.1016/j.biochi.2006.10.009] [PMID:  17125900] 
[111] 
Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med  1997; 336(15): 1046-53.
[http://dx.doi.org/10.1056/NEJM199704103361502] [PMID:  9091800] 
[112] 
Thies F, Garry JM, Yaqoob P, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet  2003; 361(9356): 477-85.
[http://dx.doi.org/10.1016/S0140-6736(03)12468-3] [PMID:  12583947] 
[113] 
von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med  1999; 130(7): 554-62.
[http://dx.doi.org/10.7326/0003-4819-130-7-199904060-00003] [PMID:  10189324] 
[114] 
Poreba M, Mostowik M, Siniarski A, et al. Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes. Cardiovasc Diabetol  2017; 16(1): 50.
[http://dx.doi.org/10.1186/s12933-017-0523-9] [PMID:  28410617] 
[115] 
Vors C, Allaire J, Marin J, et al. Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: Results from the Compared study. Atherosclerosis  2017; 257: 116-22.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.01.025] [PMID:  28131045] 
[116] 
Taleb S. Inflammation in atherosclerosis. Arch Cardiovasc Dis  2016; 109(12): 708-15.
[http://dx.doi.org/10.1016/j.acvd.2016.04.002] [PMID:  27595467] 
[117] 
Tani S, Matsuo R, Kawauchi K, Yagi T, Atsumi W, Hirayama A. A cross-sectional and longitudinal study between association of n-3 polyunsaturated fatty acids derived from fish consumption and high-density lipoprotein heterogeneity. Heart Vessels  2018; 33(5): 470-80.
[http://dx.doi.org/10.1007/s00380-017-1082-4] [PMID:  29159568] 
[118] 
Castelli WP. Cholesterol and lipids in the risk of coronary artery disease--the Framingham Heart Study. Can J Cardiol  1988; 4(Suppl A): 5A-10A.
[119] 
Sekikawa A, Mahajan H, Kadowaki S, et al. SESSA Research Group. Association of blood levels of marine omega-3 fatty acids with coronary calcification and calcium density in Japanese men. Eur J Clin Nutr  2019; 73(5): 783-92.
[http://dx.doi.org/10.1038/s41430-018-0242-7] [PMID:  30050076] 
[120] 
Tani S, Nagao K, Hirayama A. Association of atherosclerosis related markers and its relationship to n-3 polyunsaturated fatty acids levels with a prevalence of coronary artery disease in an urban area in Japan. Heart Vessels  2015; 30(1): 9-19.
[http://dx.doi.org/10.1007/s00380-013-0442-y] [PMID:  24309896] 
[121] 
Mahajan H, Choo J, Masaki K, et al. Serum long-chain n-3 polyunsaturated fatty acids and aortic calcification in middle-aged men: The population-based cross-sectional ERA-JUMP study. Nutr Metab Cardiovasc Dis  2019; 29(8): 837-46.
[http://dx.doi.org/10.1016/j.numecd.2019.04.011] [PMID:  31151884] 
[122] 
van den Born BJ. Blood pressure lowering and cardiovascular risk. Lancet  2014; 384(9956): 1746.
[http://dx.doi.org/10.1016/S0140-6736(14)62069-9] [PMID:  25455245] 
[123] 
Muntner P, Whittle J, Lynch AI, et al. Visit-to-visit variability of blood pressure and coronary heart disease, stroke, heart failure, and mortality: a cohort study. Ann Intern Med  2015; 163(5): 329-38.
[http://dx.doi.org/10.7326/M14-2803] [PMID:  26215765] 
[124] 
Gosmanova EO, Mikkelsen MK, Molnar MZ, et al. Association of systolic blood pressure variability with mortality, coronary heart disease, stroke, and renal disease. J Am Coll Cardiol  2016; 68(13): 1375-86.
[http://dx.doi.org/10.1016/j.jacc.2016.06.054] [PMID:  27659458] 
[125] 
Del Brutto OH, Mera RM, Gillman J, Castillo PR, Zambrano M, Ha JE. Dietary oily fish intake and blood pressure levels: a population-based study. J Clin Hypertens (Greenwich)  2016; 18(4): 337-41.
[http://dx.doi.org/10.1111/jch.12684] [PMID:  26395549] 
[126] 
Liu JC, Conklin SM, Manuck SB, Yao JK, Muldoon MF. Long chain omega-3 fatty acids and blood pressure. Am J Hypertens  2011; 24(10): 1121-6.
[http://dx.doi.org/10.1038/ajh.2011.120] [PMID:  21753804] 
[127] 
Miller PE, Van Elswyk M, Alexander DD. Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials. Am J Hypertens  2014; 27(7): 885-96.
[http://dx.doi.org/10.1093/ajh/hpu024] [PMID:  24610882] 
[128] 
Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens  2002; 20(8): 1493-9.
[http://dx.doi.org/10.1097/00004872-200208000-00010] [PMID:  12172309] 
[129] 
Appel LJ, Miller ER III, Seidler AJ, Whelton PK. Does supplementation of diet with ‘fish oil’ reduce blood pressure? A meta-analysis of controlled clinical trials. Arch Intern Med  1993; 153(12): 1429-38.
[http://dx.doi.org/10.1001/archinte.1993.00410120017003] [PMID:  8141868] 
[130] 
Gillum RF, Mussolino ME, Madans JH. Fish consumption and hypertension incidence in African Americans and whites: the NHANES I Epidemiologic Follow-up Study. J Natl Med Assoc  2001; 93(4): 124-8.
[PMID:  12653399] 
[131] 
Montonen J, Järvinen R, Reunanen A, Knekt P. Fish consumption and the incidence of cerebrovascular disease. Br J Nutr  2009; 102(5): 750-6.
[http://dx.doi.org/10.1017/S0007114509274782] [PMID:  19356270] 
[132] 
Yang B, Shi MQ, Li ZH, Yang JJ, Li D. Fish, long-chain n-3 pufa and incidence of elevated blood pressure: a meta-analysis of prospective cohort studies. Nutrients  2016; 8(1): 8.
[http://dx.doi.org/10.3390/nu8010058] [PMID:  26805877] 
[133] 
Sun R, Wang X, Liu Y, Xia M. Dietary supplementation with fish oil alters the expression levels of proteins governing mitochondrial dynamics and prevents high-fat diet-induced endothelial dysfunction. Br J Nutr  2014; 112(2): 145-53.
[http://dx.doi.org/10.1017/S0007114514000701] [PMID:  24775220] 
[134] 
Zeng X, Guo R, Dong M, Zheng J, Lin H, Lu H. Contribution of TLR4 signaling in intermittent hypoxia-mediated atherosclerosis progression. J Transl Med  2018; 16(1): 106.
[http://dx.doi.org/10.1186/s12967-018-1479-6] [PMID:  29673358] 
[135] 
Luchetti F, Crinelli R, Cesarini E, et al. Endothelial cells, endoplasmic reticulum stress and oxysterols. Redox Biol  2017; 13: 581-7.
[http://dx.doi.org/10.1016/j.redox.2017.07.014] [PMID:  28783588] 
[136] 
Moura-Assis A, Afonso MS, de Oliveira V, et al. Flaxseed oil rich in omega-3 protects aorta against inflammation and endoplasmic reticulum stress partially mediated by GPR120 receptor in obese, diabetic and dyslipidemic mice models. J Nutr Biochem  2018; 53: 9-19.
[http://dx.doi.org/10.1016/j.jnutbio.2017.09.015] [PMID:  29175142] 
[137] 
O’Connell TD, Block RC, Huang SP, Shearer GC. ω3-Polyunsaturated fatty acids for heart failure: Effects of dose on efficacy and novel signaling through free fatty acid receptor 4. J Mol Cell Cardiol  2017; 103: 74-92.
[http://dx.doi.org/10.1016/j.yjmcc.2016.12.003] [PMID:  27986444] 
[138] 
Tousoulis D, Kampoli AM, Tentolouris C, Papageorgiou N, Stefanadis C. The role of nitric oxide on endothelial function. Curr Vasc Pharmacol  2012; 10(1): 4-18.
[http://dx.doi.org/10.2174/157016112798829760] [PMID:  22112350] 
[139] 
Coleman HA, Tare M, Parkington HC. Endothelial potassium channels, endothelium-dependent hyperpolarization and the regulation of vascular tone in health and disease. Clin Exp Pharmacol Physiol  2004; 31(9): 641-9.
[http://dx.doi.org/10.1111/j.1440-1681.2004.04053.x] [PMID:  15479173] 
[140] 
Gousset-Dupont A, Robert V, Grynberg A, Lacour B, Tardivel S. The effect of n-3 PUFA on eNOS activity and expression in Ea hy 926 cells. Prostaglandins Leukot Essent Fatty Acids  2007; 76(3): 131-9.
[http://dx.doi.org/10.1016/j.plefa.2006.11.005] [PMID:  17229561] 
[141] 
Vu TT, Dieterich P, Vu TT, Deussen A. Docosahexaenoic acid reduces adenosine triphosphate-induced calcium influx via inhibition of store-operated calcium channels and enhances baseline endothelial nitric oxide synthase phosphorylation in human endothelial cells. Korean J Physiol Pharmacol  2019; 23(5): 345-56.
[http://dx.doi.org/10.4196/kjpp.2019.23.5.345] [PMID:  31496872] 
[142] 
Yagi S, Aihara K, Fukuda D, et al. Effects of docosahexaenoic Acid on the endothelial function in patients with coronary artery disease. J Atheroscler Thromb  2015; 22(5): 447-54.
[http://dx.doi.org/10.5551/jat.26914] [PMID:  25342567] 
[143] 
Ma DW, Seo J, Davidson LA, et al. n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon. FASEB J  2004; 18(9): 1040-2.
[http://dx.doi.org/10.1096/fj.03-1430fje] [PMID:  15084525] 
[144] 
Jump DB. The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem  2002; 277(11): 8755-8.
[http://dx.doi.org/10.1074/jbc.R100062200] [PMID:  11748246] 
[145] 
Li Q, Zhang Q, Wang M, et al. Docosahexaenoic acid affects endothelial nitric oxide synthase in caveolae. Arch Biochem Biophys  2007; 466(2): 250-9.
[http://dx.doi.org/10.1016/j.abb.2007.06.023] [PMID:  17662956] 
[146] 
Chao CY, Lii CK, Ye SY, et al. Docosahexaenoic acid inhibits vascular endothelial growth factor (VEGF)-induced cell migration via the GPR120/PP2A/ERK1/2/eNOS signaling pathway in human umbilical vein endothelial cells. J Agric Food Chem  2014; 62(18): 4152-8.
[http://dx.doi.org/10.1021/jf5007165] [PMID:  24734983] 
[147] 
Matesanz N, Park G, McAllister H, et al. Docosahexaenoic acid improves the nitroso-redox balance and reduces VEGF-mediated angiogenic signaling in microvascular endothelial cells. Invest Ophthalmol Vis Sci  2010; 51(12): 6815-25.
[http://dx.doi.org/10.1167/iovs.10-5339] [PMID:  20702831] 
[148] 
Sakai C, Ishida M, Ohba H, et al. Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells. PLoS One  2017; 12(11): e0187934.
[http://dx.doi.org/10.1371/journal.pone.0187934] [PMID:  29121093] 
[149] 
Hwang HJ, Jung TW, Kim JW, et al. Protectin DX prevents H2O2-mediated oxidative stress in vascular endothelial cells via an AMPK-dependent mechanism. Cell Signal  2019; 53: 14-21.
[http://dx.doi.org/10.1016/j.cellsig.2018.09.011] [PMID:  30244170] 
[150] 
Karbasforush S, Nourazarian A, Darabi M, et al. Docosahexaenoic acid reversed atherosclerotic changes in human endothelial cells induced by palmitic acid in vitro. Cell Biochem Funct  2018; 36(4): 203-11.
[http://dx.doi.org/10.1002/cbf.3332] [PMID:  29653462] 
[151] 
Haybar H, Shahrabi S, Rezaeeyan H, Shirzad R, Saki N. Endothelial cells: from dysfunction mechanism to pharmacological effect in cardiovascular disease. Cardiovasc Toxicol  2019; 19(1): 13-22.
[http://dx.doi.org/10.1007/s12012-018-9493-8] [PMID:  30506414] 
[152] 
Lane-Cordova AD, Kershaw K, Liu K, Herrington D, Lloyd-Jones DM. Association between cardiovascular health and endothelial function with future erectile dysfunction: the multi-ethnic study of atherosclerosis. Am J Hypertens  2017; 30(8): 815-21.
[http://dx.doi.org/10.1093/ajh/hpx060] [PMID:  28430921] 
[153] 
Okada T, Morino K, Nakagawa F, et al. N-3 Polyunsaturated fatty acids decrease the protein expression of soluble epoxide hydrolase via oxidative stress-induced p38 kinase in rat endothelial cells. Nutrients  2017; 9(7): 9.
[http://dx.doi.org/10.3390/nu9070654] [PMID:  28672788] 
[154] 
Richard D, Wolf C, Barbe U, Kefi K, Bausero P, Visioli F. Docosahexaenoic acid down-regulates endothelial Nox 4 through a sPLA2 signalling pathway. Biochem Biophys Res Commun  2009; 389(3): 516-22.
[http://dx.doi.org/10.1016/j.bbrc.2009.09.013] [PMID:  19737538] 
[155] 
Wenzel P, Rossmann H, Müller C, et al. Heme oxygenase-1 suppresses a pro-inflammatory phenotype in monocytes and determines endothelial function and arterial hypertension in mice and humans. Eur Heart J  2015; 36(48): 3437-46.
[http://dx.doi.org/10.1093/eurheartj/ehv544] [PMID:  26516175] 
[156] 
Luo Z, Aslam S, Welch WJ, Wilcox CS. Activation of nuclear factor erythroid 2-related factor 2 coordinates dimethylarginine dimethylaminohydrolase/PPAR-γ/endothelial nitric oxide synthase pathways that enhance nitric oxide generation in human glomerular endothelial cells. Hypertension  2015; 65(4): 896-902.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.04760] [PMID:  25691623] 
[157] 
Lee SE, Kim GD, Yang H, et al. Effects of eicosapentaenoic acid on the cytoprotection through Nrf2-mediated Heme Oxygenase-1 in human endothelial cells. J Cardiovasc Pharmacol  2015; 66(1): 108-17.
[http://dx.doi.org/10.1097/FJC.0000000000000251] [PMID:  25815672] 
[158] 
Delton-Vandenbroucke I, Véricel E, Januel C, Carreras M, Lecomte M, Lagarde M. Dual regulation of glutathione peroxidase by docosahexaenoic acid in endothelial cells depending on concentration and vascular bed origin. Free Radic Biol Med  2001; 30(8): 895-904.
[http://dx.doi.org/10.1016/S0891-5849(01)00482-8] [PMID:  11295532] 
[159] 
Wang C, Luo Z, Carter G, et al. NRF2 prevents hypertension, increased ADMA, microvascular oxidative stress, and dysfunction in mice with two weeks of ANG II infusion. Am J Physiol Regul Integr Comp Physiol  2018; 314(3): R399-406.
[http://dx.doi.org/10.1152/ajpregu.00122.2017] [PMID:  29167164] 
[160] 
Ooi BK, Goh BH, Yap WH. Oxidative stress in cardiovascular diseases: involvement of Nrf2 antioxidant redox signaling in macrophage foam cells formation. Int J Mol Sci  2017; 18(11): 18.
[http://dx.doi.org/10.3390/ijms18112336] [PMID:  29113088] 
[161] 
Henríquez-Olguín C, Altamirano F, Valladares D, López JR, Allen PD, Jaimovich E. Altered ROS production, NF-κB activation and interleukin-6 gene expression induced by electrical stimulation in dystrophic mdx skeletal muscle cells. Biochim Biophys Acta  2015; 1852(7): 1410-9.
[http://dx.doi.org/10.1016/j.bbadis.2015.03.012] [PMID:  25857619] 
[162] 
Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev  2006; 86(2): 515-81.
[http://dx.doi.org/10.1152/physrev.00024.2005] [PMID:  16601268] 
[163] 
Massaro M, Habib A, Lubrano L, et al. The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKC epsilon inhibition. Proc Natl Acad Sci USA  2006; 103(41): 15184-9.
[http://dx.doi.org/10.1073/pnas.0510086103] [PMID:  17018645] 
[164] 
Calder PC. The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability. Mol Nutr Food Res  2012; 56(7): 1073-80.
[http://dx.doi.org/10.1002/mnfr.201100710] [PMID:  22760980] 
[165] 
Chen H, Li D, Chen J, Roberts GJ, Saldeen T, Mehta JL. EPA and DHA attenuate ox-LDL-induced expression of adhesion molecules in human coronary artery endothelial cells via protein kinase B pathway. J Mol Cell Cardiol  2003; 35(7): 769-75.
[http://dx.doi.org/10.1016/S0022-2828(03)00120-2] [PMID:  12818567] 
[166] 
Yamagata K, Suzuki S, Tagami M. Docosahexaenoic acid prevented tumor necrosis factor alpha-induced endothelial dysfunction and senescence. Prostaglandins Leukot Essent Fatty Acids  2016; 104: 11-8.
[http://dx.doi.org/10.1016/j.plefa.2015.10.006] [PMID:  26802937] 
[167] 
Kataoka H, Kume N, Miyamoto S, et al. Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions. Circulation  1999; 99(24): 3110-7.
[http://dx.doi.org/10.1161/01.CIR.99.24.3110] [PMID:  10377073] 
[168] 
Honjo M, Nakamura K, Yamashiro K, et al. Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation. Proc Natl Acad Sci USA  2003; 100(3): 1274-9.
[http://dx.doi.org/10.1073/pnas.0337528100] [PMID:  12538855] 
[169] 
Lin HC, Lii CK, Lin AH, et al. Docosahexaenoic acid inhibits TNFα-induced ICAM-1 expression by activating PPARα and autophagy in human endothelial cells. Food Chem Toxicol  2019; 134110811
[http://dx.doi.org/10.1016/j.fct.2019.110811] [PMID:  31499122] 
[170] 
Yang YC, Lii CK, Wei YL, et al. Docosahexaenoic acid inhibition of inflammation is partially via cross-talk between Nrf2/heme oxygenase 1 and IKK/NF-κB pathways. J Nutr Biochem  2013; 24(1): 204-12.
[http://dx.doi.org/10.1016/j.jnutbio.2012.05.003] [PMID:  22901690] 
[171] 
Russo GL. Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol  2009; 77(6): 937-46.
[http://dx.doi.org/10.1016/j.bcp.2008.10.020] [PMID:  19022225] 
Rights & Permissions Print Cite
Article Metrics
17
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1381612826666200403121952	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286
Current Pharmaceutical Design

Prevention of Endothelial Dysfunction and Cardiovascular Disease by n-3 Fatty Acids-Inhibiting Action on Oxidative Stress and Inflammation

Abstract Play Pause

Related Journals

Related Books

Related Articles

Abstract
