Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Immunity, Vascular Aging and Stroke

Author(s): Anna-Maria Louka*, Dimitrios Sagris and George Ntaios

Volume 29, Issue 34, 2022

Published on: 15 March, 2022

Page: [5510 - 5521] Pages: 12

DOI: 10.2174/0929867329666220103101700

Price: $65

Abstract

Stroke is one of the most devastating manifestations of cardiovascular disease. Growing age, arterial hypertension, and atherosclerosis are identified as independent risk factors for stroke, primarily due to structural and functional alterations in the cerebrovascular tree. Recent data from in vitro and clinical studies have suggested that the immune system influences atherosclerosis, promoting vascular stiffness and vascular aging and contributing to ischemic stroke, intracranial haemorrhage and microbleeds, white matter disease, and cognitive decline. Furthermore, aging is related to a chronic low-grade inflammatory state, in which macrophage, neutrophils, natural killer (NK cells), and B and T lymphocytes act as major effectors of the immune-mediated cell responses. Moreover, oxidative stress and vascular inflammation are correlated with endothelial dysfunction, vascular aging, blood-brain barrier disruption, lacunar lesions, and neurodegenerative disorders. This review discusses the pathophysiological roles of fundamental cellular and molecular mechanisms of aging, including the complex interplay between them and innate immunity, as well as vascular dysfunction, arterial stiffness, atherosclerosis, atherothrombosis, systemic inflammation, and blood-brain barrier dysfunction.

Keywords: Innate immunity, stroke, vascular aging, vascular dysfunction, cardiovascular risk factors, blood-brain barrier.

« Previous Next »
[1]
Csiszar, A.; Ungvari, Z.; Edwards, J.G.; Kaminski, P.; Wolin, M.S.; Koller, A.; Kaley, G. Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ. Res., 2002, 90(11), 1159-1166.
[http://dx.doi.org/10.1161/01.RES.0000020401.61826.EA] [PMID: 12065318]
[2]
Lawes, C.M.M.; Bennett, D.A.; Feigin, V.L.; Rodgers, A. Blood pressure and stroke: An overview of published reviews. Stroke, 2004, 35(3), 776-785.
[http://dx.doi.org/10.1161/01.STR.0000116869.64771.5A] [PMID: 14976329]
[3]
Nilsson, P.M.; Boutouyrie, P.; Laurent, S. Vascular aging: A tale of EVA and ADAM in cardiovascular risk assessment and prevention. Hypertension, 2009, 54(1), 3-10.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.129114] [PMID: 19487587]
[4]
Medzhitov, R. Origin and physiological roles of inflammation. Nature, 2008, 454(7203), 428-435.
[http://dx.doi.org/10.1038/nature07201] [PMID: 18650913]
[5]
Barrett, T.J. Macrophages in atherosclerosis regression. Arterioscler. Thromb. Vasc. Biol., 2020, 40(1), 20-33.
[http://dx.doi.org/10.1161/ATVBAHA.119.312802] [PMID: 31722535]
[6]
McLaughlin, T.; Liu, L-F.; Lamendola, C.; Shen, L.; Morton, J.; Rivas, H.; Winer, D.; Tolentino, L.; Choi, O.; Zhang, H.; Chng, H.Y.M.; Engleman, E. T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arterioscler. Thromb. Vasc. Biol., 2014, 34(12), 2637-2643.
[http://dx.doi.org/10.1161/ATVBAHA.114.304636] [PMID: 25341798]
[7]
Sage, A.P.; Tsiantoulas, D.; Binder, C.J.; Mallat, Z. The role of B cells in atherosclerosis. Nat. Rev. Cardiol., 2019, 16(3), 180-196.
[http://dx.doi.org/10.1038/s41569-018-0106-9] [PMID: 30410107]
[8]
Rundberg Nilsson, A.; Soneji, S.; Adolfsson, S.; Bryder, D.; Pronk, C.J. Human and murine hematopoietic stem cell aging is associated with functional impairments and intrinsic megakaryocytic/erythroid bias. PLoS One, 2016, 11(7), e0158369.
[http://dx.doi.org/10.1371/journal.pone.0158369] [PMID: 27368054]
[9]
Cheshier, S.H.; Morrison, S.J.; Liao, X.; Weissman, I.L. In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc. Natl. Acad. Sci. USA, 1999, 96(6), 3120-3125.
[http://dx.doi.org/10.1073/pnas.96.6.3120] [PMID: 10077647]
[10]
Chambers, S.M.; Shaw, C.A.; Gatza, C.; Fisk, C.J.; Donehower, L.A.; Goodell, M.A. Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol., 2007, 5(8), e201.
[http://dx.doi.org/10.1371/journal.pbio.0050201] [PMID: 17676974]
[11]
Harris, T.B.; Ferrucci, L.; Tracy, R.P. Associations of elevated Interleukin-6 and C-Reactive protein levels with mortality in the elderly. Am. J. Med., 1999, 106(5), 506-512.
[http://dx.doi.org/10.1016/S0002-9343(99)00066-2]
[12]
Mejias, N.H.; Martinez, C.C.; Stephens, M.E.; de Rivero Vaccari, J.P. Contribution of the inflammasome to inflammaging. J. Inflamm. (Lond.), 2018, 15(1), 23.
[http://dx.doi.org/10.1186/s12950-018-0198-3] [PMID: 30473634]
[13]
Lumeng, C.N.; Liu, J.; Geletka, L.; Delaney, C.; Delproposto, J.; Desai, A.; Oatmen, K.; Martinez-Santibanez, G.; Julius, A.; Garg, S.; Yung, R.L. Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue. J. Immunol., 2011, 187(12), 6208-6216.
[http://dx.doi.org/10.4049/jimmunol.1102188] [PMID: 22075699]
[14]
Wu, D.; Ren, Z.; Pae, M.; Guo, W.; Cui, X.; Merrill, A.H.; Meydani, S.N. Aging up-regulates expression of inflammatory mediators in mouse adipose tissue. J. Immunol., 2007, 179(7), 4829-4839.
[http://dx.doi.org/10.4049/jimmunol.179.7.4829] [PMID: 17878382]
[15]
Jaiswal, S.; Fontanillas, P.; Flannick, J.; Manning, A.; Grauman, P.V.; Mar, B.G.; Lindsley, R.C.; Mermel, C.H.; Burtt, N.; Chavez, A.; Higgins, J.M.; Moltchanov, V.; Kuo, F.C.; Kluk, M.J.; Henderson, B.; Kinnunen, L.; Koistinen, H.A.; Ladenvall, C.; Getz, G.; Correa, A.; Banahan, B.F.; Gabriel, S.; Kathiresan, S.; Stringham, H.M.; McCarthy, M.I.; Boehnke, M.; Tuomilehto, J.; Haiman, C.; Groop, L.; Atzmon, G.; Wilson, J.G.; Neuberg, D.; Altshuler, D.; Ebert, B.L. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med., 2014, 371(26), 2488-2498.
[http://dx.doi.org/10.1056/NEJMoa1408617] [PMID: 25426837]
[16]
Jaiswal, S.; Natarajan, P.; Silver, A.J.; Gibson, C.J.; Bick, A.G.; Shvartz, E.; McConkey, M.; Gupta, N.; Gabriel, S.; Ardissino, D.; Baber, U.; Mehran, R.; Fuster, V.; Danesh, J.; Frossard, P.; Saleheen, D.; Melander, O.; Sukhova, G.K.; Neuberg, D.; Libby, P.; Kathiresan, S.; Ebert, B.L. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N. Engl. J. Med., 2017, 377(2), 111-121.
[http://dx.doi.org/10.1056/NEJMoa1701719] [PMID: 28636844]
[17]
Madjid, M.; Awan, I.; Willerson, J.T.; Casscells, S.W. Leukocyte count and coronary heart disease: Implications for risk assessment. J. Am. Coll. Cardiol., 2004, 44(10), 1945-1956.
[http://dx.doi.org/10.1016/j.jacc.2004.07.056] [PMID: 15542275]
[18]
Carobbio, A.; Finazzi, G.; Guerini, V.; Spinelli, O.; Delaini, F.; Marchioli, R.; Borrelli, G.; Rambaldi, A.; Barbui, T. Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: Interaction with treatment, standard risk factors, and Jak2 mutation status. Blood, 2007, 109(6), 2310-2313.
[http://dx.doi.org/10.1182/blood-2006-09-046342] [PMID: 17110452]
[19]
Wang, W.; Liu, W.; Fidler, T.; Wang, Y.; Tang, Y.; Woods, B.; Welch, C.; Cai, B.; Silvestre-Roig, C.; Ai, D.; Yang, Y.G.; Hidalgo, A.; Soehnlein, O.; Tabas, I.; Levine, R.L.; Tall, A.R.; Wang, N. Macrophage inflammation, erythrophagocytosis, and accelerated atherosclerosis in Jak2 V617F mice. Circ. Res., 2018, 123(11), e35-e47.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.313283] [PMID: 30571460]
[20]
Wolach, O.; Sellar, R.S.; Martinod, K.; Cherpokova, D.; McConkey, M.; Chappell, R.J.; Silver, A.J.; Adams, D.; Castellano, C.A.; Schneider, R.K.; Padera, R.F.; DeAngelo, D.J.; Wadleigh, M.; Steensma, D.P.; Galinsky, I.; Stone, R.M.; Genovese, G.; McCarroll, S.A.; Iliadou, B.; Hultman, C.; Neuberg, D.; Mullally, A.; Wagner, D.D.; Ebert, B.L. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Sci. Transl. Med., 2018, 10(436), eaan8292.
[http://dx.doi.org/10.1126/scitranslmed.aan8292] [PMID: 29643232]
[21]
Barbosa, M.C.; Grosso, R.A.; Fader, C.M. Hallmarks of aging: An autophagic perspective. Front. Endocrinol. (Lausanne), 2019, 9, 790.
[http://dx.doi.org/10.3389/fendo.2018.00790] [PMID: 30687233]
[22]
Tyrrell, D.J.; Goldstein, D.R. Ageing and atherosclerosis: Vascular intrinsic and extrinsic factors and potential role of IL-6. Int. Rev. Cell Mol. Biol., 2018, 340, 209-344.
[http://dx.doi.org/10.1038/s41569-020-0431-7] [PMID: 32918047]
[23]
Giorgi, C.; Marchi, S.; Simoes, I.C.M. Mitochondria and reactive oxygen species in aging and age-related diseases. 2018.
[http://dx.doi.org/10.1016/bs.ircmb.2018.05.006]
[24]
Swiader, A.; Nahapetyan, H.; Faccini, J.; D’Angelo, R.; Mucher, E.; Elbaz, M.; Boya, P.; Vindis, C. Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids. Oncotarget, 2016, 7(20), 28821-28835.
[http://dx.doi.org/10.18632/oncotarget.8936] [PMID: 27119505]
[25]
Huang, L.S.; Hong, Z.; Wu, W.; Xiong, S.; Zhong, M.; Gao, X.; Rehman, J.; Malik, A.B. mtDNA activates cGAS signaling and suppresses the YAP-mediated endothelial cell proliferation program to promote inflammatory injury. Immunity, 2020, 52(3), 475-486.e5.
[http://dx.doi.org/10.1016/j.immuni.2020.02.002] [PMID: 32164878]
[26]
Misra, M.K.; Sarwat, M.; Bhakuni, P.; Tuteja, R.; Tuteja, N. Oxidative stress and ischemic myocardial syndromes. Med. Sci. Monit., 2009, 15(10), RA209-RA219.
[PMID: 19789524]
[27]
Ross, R. Atherosclerosis-an inflammatory disease. N. Engl. J. Med., 1999, 340(2), 115-126.
[http://dx.doi.org/10.1056/NEJM199901143400207] [PMID: 9887164]
[28]
Shashkin, P.; Dragulev, B.; Ley, K. Macrophage differentiation to foam cells. Curr. Pharm. Des., 2005, 11(23), 3061-3072.
[http://dx.doi.org/10.2174/1381612054865064] [PMID: 16178764]
[29]
Tajbakhsh, A.; Rezaee, M.; Kovanen, P.T.; Sahebkar, A. Efferocytosis in atherosclerotic lesions: Malfunctioning regulatory pathways and control mechanisms. Pharmacol. Ther., 2018, 188, 12-25.
[http://dx.doi.org/10.1016/j.pharmthera.2018.02.003] [PMID: 29444453]
[30]
Zimmer, S.; Grebe, A.; Latz, E. Danger signaling in atherosclerosis. Circ. Res., 2015, 116(2), 323-340.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.301135] [PMID: 25593277]
[31]
Guo, H.; Callaway, J.B.; Ting, J.P-Y. Inflammasomes: Mechanism of action, role in disease, and therapeutics. Nat. Med., 2015, 21(7), 677-687.
[http://dx.doi.org/10.1038/nm.3893] [PMID: 26121197]
[32]
Arango Duque, G.; Descoteaux, A. Macrophage cytokines: Involvement in immunity and infectious diseases. Front. Immunol., 2014, 5, 491.
[http://dx.doi.org/10.3389/fimmu.2014.00491] [PMID: 25339958]
[33]
Lee, D.C.; Ruiz, C.R.; Lebson, L.; Selenica, M.L.; Rizer, J.; Hunt, J.B., Jr; Rojiani, R.; Reid, P.; Kammath, S.; Nash, K.; Dickey, C.A.; Gordon, M.; Morgan, D. Aging enhances classical activation but mitigates alternative activation in the central nervous system. Neurobiol. Aging, 2013, 34(6), 1610-1620.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.12.014] [PMID: 23481567]
[34]
Sendama, W. The effect of ageing on the resolution of inflammation. Ageing Res. Rev., 2020, 57, 101000.
[http://dx.doi.org/10.1016/j.arr.2019.101000] [PMID: 31862417]
[35]
Gaya da Costa, M.; Poppelaars, F.; van Kooten, C.; Mollnes, T.E.; Tedesco, F.; Würzner, R.; Trouw, L.A.; Truedsson, L.; Daha, M.R.; Roos, A.; Seelen, M.A. Age and sex-associated changes of complement activity and complement levels in a healthy caucasian population. Front. Immunol., 2018, 9, 2664.
[http://dx.doi.org/10.3389/fimmu.2018.02664] [PMID: 30515158]
[36]
Hayashi, F.; Means, T.K.; Luster, A.D. Toll-like receptors stimulate human neutrophil function. Blood, 2003, 102(7), 2660-2669.
[http://dx.doi.org/10.1182/blood-2003-04-1078] [PMID: 12829592]
[37]
Thålin, C.; Hisada, Y.; Lundström, S.; Mackman, N.; Wallén, H. Neutrophil extracellular traps: Villains and targets in arterial, venous, and cancer-associated thrombosis. Arterioscler. Thromb. Vasc. Biol., 2019, 39(9), 1724-1738.
[http://dx.doi.org/10.1161/ATVBAHA.119.312463] [PMID: 31315434]
[38]
Denny, M.F.; Yalavarthi, S.; Zhao, W.; Thacker, S.G.; Anderson, M.; Sandy, A.R.; McCune, W.J.; Kaplan, M.J. A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs. J. Immunol., 2010, 184(6), 3284-3297.
[http://dx.doi.org/10.4049/jimmunol.0902199] [PMID: 20164424]
[39]
Stakos, D.A.; Kambas, K.; Konstantinidis, T.; Mitroulis, I.; Apostolidou, E.; Arelaki, S.; Tsironidou, V.; Giatromanolaki, A.; Skendros, P.; Konstantinides, S.; Ritis, K. Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction. Eur. Heart J., 2015, 36(22), 1405-1414.
[http://dx.doi.org/10.1093/eurheartj/ehv007] [PMID: 25660055]
[40]
Peña-Martínez, C.; Durán-Laforet, V.; García-Culebras, A.; Ostos, F.; Hernández-Jiménez, M.; Bravo-Ferrer, I.; Pérez-Ruiz, A.; Ballenilla, F.; Díaz-Guzmán, J.; Pradillo, J.M.; Lizasoain, I.; Moro, M.A. Pharmacological modulation of neutrophil extracellular traps reverses thrombotic stroke tpa (tissue-type plasminogen activator) resistance. Stroke, 2019, 50(11), 3228-3237.
[http://dx.doi.org/10.1161/STROKEAHA.119.026848] [PMID: 31526124]
[41]
Weng, N.P. Aging of the immune system: How much can the adaptive immune system adapt? Immunity, 2006, 24(5), 495-499.
[http://dx.doi.org/10.1016/j.immuni.2006.05.001] [PMID: 16713964]
[42]
Lahoute, C.; Herbin, O.; Mallat, Z.; Tedgui, A. Adaptive immunity in atherosclerosis: Mechanisms and future therapeutic targets. Nat. Rev. Cardiol., 2011, 8(6), 348-358.
[http://dx.doi.org/10.1038/nrcardio.2011.62] [PMID: 21502963]
[43]
Libby, P.; Ridker, P.M.; Hansson, G.K. Progress and challenges in translating the biology of atherosclerosis. Nature, 2011, 473(7347), 317-325.
[http://dx.doi.org/10.1038/nature10146] [PMID: 21593864]
[44]
Mallat, Z.; Taleb, S.; Ait-Oufella, H.; Tedgui, A. The role of adaptive T cell immunity in atherosclerosis. J. Lipid Res., 2009, 50(Suppl.), S364-S369.
[http://dx.doi.org/10.1194/jlr.R800092-JLR200] [PMID: 19050311]
[45]
Whitman, S.C.; Ravisankar, P.; Elam, H.; Daugherty, A. Exogenous interferon-γ enhances atherosclerosis in apolipoprotein E-/- mice. Am. J. Pathol., 2000, 157(6), 1819-1824.
[http://dx.doi.org/10.1016/S0002-9440(10)64820-1] [PMID: 11106554]
[46]
Engelbertsen, D.; Andersson, L.; Ljungcrantz, I.; Wigren, M.; Hedblad, B.; Nilsson, J.; Björkbacka, H. T-helper 2 immunity is associated with reduced risk of myocardial infarction and stroke. Arterioscler. Thromb. Vasc. Biol., 2013, 33(3), 637-644.
[http://dx.doi.org/10.1161/ATVBAHA.112.300871] [PMID: 23307873]
[47]
Subramanian, M.; Thorp, E.; Hansson, G.K.; Tabas, I. Treg-mediated suppression of atherosclerosis requires MYD88 signaling in DCs. J. Clin. Invest., 2013, 275, E21-E22.
[http://dx.doi.org/10.1172/JCI64617] [PMID: 23257360]
[48]
Moregola, A.; Bonacina, F.; Coe, D.J. Impact of LDL receptor on lymphocytes T cell differentiation and function. Atherosclerosis, 2018, 275
[http://dx.doi.org/10.1016/j.atherosclerosis.2018.06.049]
[49]
Frostegård, J.; Huang, Y.H.; Rönnelid, J.; Schäfer-Elinder, L. Platelet-activating factor and oxidized LDL induce immune activation by a common mechanism. Arterioscler. Thromb. Vasc. Biol., 1997, 17(5), 963-968.
[http://dx.doi.org/10.1161/01.ATV.17.5.963] [PMID: 9157962]
[50]
Hansson, G.K.; Jonasson, L.; Lojsthed, B.; Stemme, S.; Kocher, O.; Gabbiani, G. Localization of T lymphocytes and macrophages in fibrous and complicated human atherosclerotic plaques. Atherosclerosis, 1988, 72(2-3), 135-141.
[http://dx.doi.org/10.1016/0021-9150(88)90074-3] [PMID: 3063267]
[51]
Winkels, H.; Ehinger, E.; Ghosheh, Y.; Wolf, D.; Ley, K. Atherosclerosis in the single-cell era. Curr. Opin. Lipidol., 2018, 29(5), 389-396.
[http://dx.doi.org/10.1097/MOL.0000000000000537] [PMID: 30020199]
[52]
Wolf, D.; Ley, K. Immunity and inflammation in atherosclerosis. Circ. Res., 2019, 124(2), 315-327.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.313591] [PMID: 30653442]
[53]
Tsimikas, S.; Brilakis, E.S.; Lennon, R.J.; Miller, E.R.; Witztum, J.L.; McConnell, J.P.; Kornman, K.S.; Berger, P.B. Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events. J. Lipid Res., 2007, 48(2), 425-433.
[http://dx.doi.org/10.1194/jlr.M600361-JLR200] [PMID: 17093289]
[54]
AlGhatrif, M.; Strait, J.B.; Morrell, C.H.; Canepa, M.; Wright, J.; Elango, P.; Scuteri, A.; Najjar, S.S.; Ferrucci, L.; Lakatta, E.G. Longitudinal trajectories of arterial stiffness and the role of blood pressure: The Baltimore Longitudinal study of aging. Hypertension, 2013, 62(5), 934-941.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01445] [PMID: 24001897]
[55]
Ong, K.L.; Cheung, B.M.Y.; Man, Y.B.; Lau, C.P.; Lam, K.S.L. Prevalence, awareness, treatment, and control of hypertension among United States adults 1999-2004. Hypertension, 2007, 49(1), 69-75.
[http://dx.doi.org/10.1161/01.HYP.0000252676.46043.18] [PMID: 17159087]
[56]
Donato, A.J.; Eskurza, I.; Silver, A.E.; Levy, A.S.; Pierce, G.L.; Gates, P.E.; Seals, D.R. Direct evidence of endothelial oxidative stress with aging in humans: Relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB. Circ. Res., 2007, 100(11), 1659-1666.
[http://dx.doi.org/10.1161/01.RES.0000269183.13937.e8] [PMID: 17478731]
[57]
Mitchell, G.F. Arterial stiffness and hypertension. Hypertension, 2014, 64(1), 13-18.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.00921] [PMID: 24752432]
[58]
Laurent, S.; Cockcroft, J.; Van Bortel, L.; Boutouyrie, P.; Giannattasio, C.; Hayoz, D.; Pannier, B.; Vlachopoulos, C.; Wilkinson, I.; Struijker-Boudier, H. Expert consensus document on arterial stiffness: Methodological issues and clinical applications. Eur. Heart J., 2006, 27(21), 2588-2605.
[http://dx.doi.org/10.1093/eurheartj/ehl254] [PMID: 17000623]
[59]
Karras, A.; Haymann, J-P.; Bozec, E.; Metzger, M.; Jacquot, C.; Maruani, G.; Houillier, P.; Froissart, M.; Stengel, B.; Guardiola, P.; Laurent, S.; Boutouyrie, P.; Briet, M. Large artery stiffening and remodeling are independently associated with all-cause mortality and cardiovascular events in chronic kidney disease. Hypertension, 2012, 60(6), 1451-1457.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.112.197210] [PMID: 23090769]
[60]
Hashimoto, J.; Ito, S. Central pulse pressure and aortic stiffness determine renal hemodynamics: Pathophysiological implication for microalbuminuria in hypertension. Hypertension, 2011, 58(5), 839-846.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.177469] [PMID: 21968753]
[61]
Hashimoto, J.; Ito, S. Aortic stiffness determines diastolic blood flow reversal in the descending thoracic aorta: Potential implication for retrograde embolic stroke in hypertension. Hypertension, 2013, 62(3), 542-549.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01318] [PMID: 23798349]
[62]
Guzik, T.J.; Touyz, R.M. Oxidative stress, inflammation, and vascular aging in hypertension. Hypertension, 2017, 70(4), 660-667.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.07802] [PMID: 28784646]
[63]
Lacolley, P.; Challande, P.; Osborne-Pellegrin, M.; Regnault, V. Genetics and pathophysiology of arterial stiffness. Cardiovasc. Res., 2009, 81(4), 637-648.
[http://dx.doi.org/10.1093/cvr/cvn353] [PMID: 19098299]
[64]
Ungvari, Z.; Kaley, G.; de Cabo, R.; Sonntag, W.E.; Csiszar, A. Mechanisms of vascular aging: New perspectives. J. Gerontol. A Biol. Sci. Med. Sci., 2010, 65(10), 1028-1041.
[http://dx.doi.org/10.1093/gerona/glq113] [PMID: 20576649]
[65]
Luft, F.C. Molecular mechanisms of arterial stiffness: New insights. J. Am. Soc. Hypertens., 2012, 6(6), 436-438.
[http://dx.doi.org/10.1016/j.jash.2012.10.004] [PMID: 23199674]
[66]
Youn, J-C.; Yu, H.T.; Lim, B.J.; Koh, M.J.; Lee, J.; Chang, D.Y.; Choi, Y.S.; Lee, S.H.; Kang, S.M.; Jang, Y.; Yoo, O.J.; Shin, E.C.; Park, S. Immunosenescent CD8+ T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension. Hypertension, 2013, 62(1), 126-133.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.00689] [PMID: 23716586]
[67]
Sehgel, N.L.; Sun, Z.; Hong, Z.; Hunter, W.C.; Hill, M.A.; Vatner, D.E.; Vatner, S.F.; Meininger, G.A. Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging. Hypertension, 2015, 65(2), 370-377.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.04456] [PMID: 25452471]
[68]
Ayuzawa, N.; Nagase, M.; Ueda, K.; Nishimoto, M.; Kawarazaki, W.; Marumo, T.; Aiba, A.; Sakurai, T.; Shindo, T.; Fujita, T. Rac1-mediated activation of mineralocorticoid receptor in pressure overload-induced cardiac injury. Hypertension, 2016, 67(1), 99-106.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.06054] [PMID: 26527051]
[69]
Boutouyrie, P.; Tropeano, A.I.; Asmar, R.; Gautier, I.; Benetos, A.; Lacolley, P.; Laurent, S. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: A longitudinal study. Hypertension, 2002, 39(1), 10-15.
[http://dx.doi.org/10.1161/hy0102.099031] [PMID: 11799071]
[70]
Laurent, S.; Katsahian, S.; Fassot, C.; Tropeano, A.I.; Gautier, I.; Laloux, B.; Boutouyrie, P. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke, 2003, 34(5), 1203-1206.
[http://dx.doi.org/10.1161/01.STR.0000065428.03209.64] [PMID: 12677025]
[71]
Wu, S.; Jin, C.; Li, S.; Zheng, X.; Zhang, X.; Cui, L.; Gao, X. Aging, arterial stiffness, and blood pressure association in chinese adults. Hypertension, 2019, 73(4), 893-899.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.12396] [PMID: 30776974]
[72]
O’Rourke, M.F.; Nichols, W.W. Aortic diameter, aortic stiffness, and wave reflection increase with age and isolated systolic hypertension. Hypertension, 2005, 45(4), 652-658.
[http://dx.doi.org/10.1161/01.HYP.0000153793.84859.b8] [PMID: 15699456]
[73]
Elkind, M.S.V. Inflammatory mechanisms of stroke. Stroke, 2010, 41(10), S3-S8.
[http://dx.doi.org/10.1161/STROKEAHA.110.594945] [PMID: 20876499]
[74]
Kiechl, S.; Egger, G.; Mayr, M.; Wiedermann, C.J.; Bonora, E.; Oberhollenzer, F.; Muggeo, M.; Xu, Q.; Wick, G.; Poewe, W.; Willeit, J. Chronic infections and the risk of carotid atherosclerosis: Prospective results from a large population study. Circulation, 2001, 103(8), 1064-1070.
[http://dx.doi.org/10.1161/01.CIR.103.8.1064] [PMID: 11222467]
[75]
Roivainen, M.; Viik-Kajander, M.; Palosuo, T.; Toivanen, P.; Leinonen, M.; Saikku, P.; Tenkanen, L.; Manninen, V.; Hovi, T.; Mänttäri, M. Infections, inflammation, and the risk of coronary heart disease. Circulation, 2000, 101(3), 252-257.
[http://dx.doi.org/10.1161/01.CIR.101.3.252] [PMID: 10645920]
[76]
Wu, T.; Trevisan, M.; Genco, R.J.; Dorn, J.P.; Falkner, K.L.; Sempos, C.T. Periodontal disease and risk of cerebrovascular disease: The first national health and nutrition examination survey and its follow-up study. Arch. Intern. Med., 2000, 160(18), 2749-2755.
[http://dx.doi.org/10.1001/archinte.160.18.2749] [PMID: 11025784]
[77]
Syrjänen, J.; Peltola, J.; Valtonen, V.; Iivanainen, M.; Kaste, M.; Huttunen, J.K. Dental infections in association with cerebral infarction in young and middle-aged men. J. Intern. Med., 1989, 225(3), 179-184.
[http://dx.doi.org/10.1111/j.1365-2796.1989.tb00060.x] [PMID: 2703800]
[78]
Grau, A.J.; Buggle, F.; Ziegler, C.; Schwarz, W.; Meuser, J.; Tasman, A.J.; Bühler, A.; Benesch, C.; Becher, H.; Hacke, W. Association between acute cerebrovascular ischemia and chronic and recurrent infection. Stroke, 1997, 28(9), 1724-1729.
[http://dx.doi.org/10.1161/01.STR.28.9.1724] [PMID: 9303015]
[79]
Bahouth, M.N.; Venkatesan, A. Acute viral illnesses and ischemic stroke: Pathophysiological considerations in the era of the COVID-19 pandemic. Stroke, 2021, 52(5), 1885-1894.
[http://dx.doi.org/10.1161/STROKEAHA.120.030630] [PMID: 33794653]
[80]
Sagris, D.; Papanikolaou, A.; Kvernland, A.; Korompoki, E.; Frontera, J.A.; Troxel, A.B.; Gavriatopoulou, M.; Milionis, H.; Lip, G.Y.H.; Michel, P.; Yaghi, S.; Ntaios, G. COVID-19 and ischemic stroke. Eur. J. Neurol., 2021, 28(11), 3826-3836.
[http://dx.doi.org/10.1111/ene.15008] [PMID: 34224187]
[81]
Sierra, A.; Gottfried-Blackmore, A.C.; McEwen, B.S.; Bulloch, K. Microglia derived from aging mice exhibit an altered inflammatory profile. Glia, 2007, 55(4), 412-424.
[http://dx.doi.org/10.1002/glia.20468] [PMID: 17203473]
[82]
Zlokovic, B.V. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat. Rev. Neurosci., 2011, 12(12), 723-738.
[http://dx.doi.org/10.1038/nrn3114] [PMID: 22048062]
[83]
Kigerl, K.A.; de Rivero Vaccari, J.P.; Dietrich, W.D.; Popovich, P.G.; Keane, R.W. Pattern recognition receptors and central nervous system repair. Exp. Neurol., 2014, 258(258), 5-16.
[http://dx.doi.org/10.1016/j.expneurol.2014.01.001] [PMID: 25017883]
[84]
Kalaria, R.N.; Kenny, R.A.; Ballard, C.G.; Perry, R.; Ince, P.; Polvikoski, T. Towards defining the neuropathological substrates of vascular dementia. J. Neurol. Sci., 2004, 226(1-2), 75-80.
[http://dx.doi.org/10.1016/j.jns.2004.09.019] [PMID: 15537525]
[85]
Shi, K.; Tian, D-C.; Li, Z-G.; Ducruet, A.F.; Lawton, M.T.; Shi, F.D. Global brain inflammation in stroke. Lancet Neurol., 2019, 18(11), 1058-1066.
[http://dx.doi.org/10.1016/S1474-4422(19)30078-X] [PMID: 31296369]
[86]
Levine, D.A.; Galecki, A.T.; Langa, K.M.; Unverzagt, F.W.; Kabeto, M.U.; Giordani, B.; Wadley, V.G. Trajectory of cognitive decline after incident stroke. JAMA, 2015, 314(1), 41-51.
[http://dx.doi.org/10.1001/jama.2015.6968] [PMID: 26151265]
[87]
Kalaria, R.N. Cerebrovascular disease and mechanisms of cognitive impairment: Evidence from clinicopathological studies in humans. Stroke, 2012, 43(9), 2526-2534.
[http://dx.doi.org/10.1161/STROKEAHA.112.655803] [PMID: 22879100]
[88]
Ridker, P.M.; Everett, B.M.; Thuren, T.; MacFadyen, J.G.; Chang, W.H.; Ballantyne, C.; Fonseca, F.; Nicolau, J.; Koenig, W.; Anker, S.D.; Kastelein, J.J.P.; Cornel, J.H.; Pais, P.; Pella, D.; Genest, J.; Cifkova, R.; Lorenzatti, A.; Forster, T.; Kobalava, Z.; Vida-Simiti, L.; Flather, M.; Shimokawa, H.; Ogawa, H.; Dellborg, M.; Rossi, P.R.F.; Troquay, R.P.T.; Libby, P.; Glynn, R.J. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med., 2017, 377(12), 1119-1131.
[http://dx.doi.org/10.1056/NEJMoa1707914] [PMID: 28845751]
[89]
Tardif, J-C.; Kouz, S.; Waters, D.D.; Bertrand, O.F.; Diaz, R.; Maggioni, A.P.; Pinto, F.J.; Ibrahim, R.; Gamra, H.; Kiwan, G.S.; Berry, C.; López-Sendón, J.; Ostadal, P.; Koenig, W.; Angoulvant, D.; Grégoire, J.C.; Lavoie, M.A.; Dubé, M.P.; Rhainds, D.; Provencher, M.; Blondeau, L.; Orfanos, A.; L’Allier, P.L.; Guertin, M.C.; Roubille, F. Efficacy and safety of low-dose colchicine after myocardial infarction. N. Engl. J. Med., 2019, 381(26), 2497-2505.
[http://dx.doi.org/10.1056/NEJMoa1912388] [PMID: 31733140]
[90]
Tardif, J-C.; McMurray, J.J.; Klug, E.; Small, R.; Schumi, J.; Choi, J.; Cooper, J.; Scott, R.; Lewis, E.F.; L’Allier, P.L.; Pfeffer, M.A. Effects of succinobucol (AGI-1067) after an acute coronary syndrome: A randomised, double-blind, placebo-controlled trial. Lancet, 2008, 371(9626), 1761-1768.
[http://dx.doi.org/10.1016/S0140-6736(08)60763-1] [PMID: 18502300]
[91]
Stähli, B.E.; Gebhard, C.; Duchatelle, V.; Cournoyer, D.; Petroni, T.; Tanguay, J.F.; Robb, S.; Mann, J.; Guertin, M.C.; Wright, R.S.; L L’Allier, P.; Tardif, J.C. Effects of the p-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention according to timing of infusion: Insights from the select-acs trial. J. Am. Heart Assoc., 2016, 5(11), e004255.
[http://dx.doi.org/10.1161/JAHA.116.004255] [PMID: 27852589]
[92]
Ridker, P.M.; Everett, B.M.; Pradhan, A.; MacFadyen, J.G.; Solomon, D.H.; Zaharris, E.; Mam, V.; Hasan, A.; Rosenberg, Y.; Iturriaga, E.; Gupta, M.; Tsigoulis, M.; Verma, S.; Clearfield, M.; Libby, P.; Goldhaber, S.Z.; Seagle, R.; Ofori, C.; Saklayen, M.; Butman, S.; Singh, N.; Le May, M.; Bertrand, O.; Johnston, J.; Paynter, N.P.; Glynn, R.J. Low-dose methotrexate for the prevention of atherosclerotic events. N. Engl. J. Med., 2019, 380(8), 752-762.
[http://dx.doi.org/10.1056/NEJMoa1809798] [PMID: 30415610]
[93]
Lehrer-Graiwer, J.; Singh, P.; Abdelbaky, A.; Vucic, E.; Korsgren, M.; Baruch, A.; Fredrickson, J.; van Bruggen, N.; Tang, M.T.; Frendeus, B.; Rudd, J.H.F.; Hsieh, F.; Ballantyne, C.M.; Ghoshhajra, B.; Rosenson, R.S.; Koren, M.; Roth, E.M.; Duprez, D.A.; Fayad, Z.A.; Tawakol, A.A. FDG-PET imaging for oxidized LDL in stable atherosclerotic disease: A phase II study of safety, tolerability, and anti-inflammatory activity. JACC Cardiovasc. Imaging, 2015, 8(4), 493-494.
[http://dx.doi.org/10.1016/j.jcmg.2014.06.021] [PMID: 25457756]
[94]
Abbate, A.; Trankle, C.R.; Buckley, L.F.; Lipinski, M.J.; Appleton, D.; Kadariya, D.; Canada, J.M.; Carbone, S.; Roberts, C.S.; Abouzaki, N.; Melchior, R.; Christopher, S.; Turlington, J.; Mueller, G.; Garnett, J.; Thomas, C.; Markley, R.; Wohlford, G.F.; Puckett, L.; Medina de Chazal, H.; Chiabrando, J.G.; Bressi, E.; Del Buono, M.G.; Schatz, A.; Vo, C.; Dixon, D.L.; Biondi-Zoccai, G.G.; Kontos, M.C.; Van Tassell, B.W. Interleukin-1 blockade inhibits the acute inflammatory response in patients with st-segment–elevation myocardial infarction. J. Am. Heart Assoc., 2020, 9(5), e014941.
[http://dx.doi.org/10.1161/JAHA.119.014941] [PMID: 32122219]
[95]
Giles, J.T.; Sattar, N.; Gabriel, S.; Ridker, P.M.; Gay, S.; Warne, C.; Musselman, D.; Brockwell, L.; Shittu, E.; Klearman, M.; Fleming, T.R. Cardiovascular safety of tocilizumab versus etanercept in rheumatoid arthritis: A randomized controlled trial. Arthritis Rheumatol., 2020, 72(1), 31-40.
[http://dx.doi.org/10.1002/art.41095] [PMID: 31469238]
[96]
Nicholls, S.J.; Kastelein, J.J.P.; Schwartz, G.G.; Bash, D.; Rosenson, R.S.; Cavender, M.A.; Brennan, D.M.; Koenig, W.; Jukema, J.W.; Nambi, V.; Wright, R.S.; Menon, V.; Lincoff, A.M.; Nissen, S.E. Varespladib and cardiovascular events in patients with an acute coronary syndrome: The VISTA-16 randomized clinical trial. JAMA, 2014, 311(3), 252-262.
[http://dx.doi.org/10.1001/jama.2013.282836] [PMID: 24247616]
[97]
White, H.D.; Held, C.; Stewart, R.; Tarka, E.; Brown, R.; Davies, R.Y.; Budaj, A.; Harrington, R.A.; Steg, P.G.; Ardissino, D.; Armstrong, P.W.; Avezum, A.; Aylward, P.E.; Bryce, A.; Chen, H.; Chen, M.F.; Corbalan, R.; Dalby, A.J.; Danchin, N.; De Winter, R.J.; Denchev, S.; Diaz, R.; Elisaf, M.; Flather, M.D.; Goudev, A.R.; Granger, C.B.; Grinfeld, L.; Hochman, J.S.; Husted, S.; Kim, H.S.; Koenig, W.; Linhart, A.; Lonn, E.; López-Sendón, J.; Manolis, A.J.; Mohler, E.R., III; Nicolau, J.C.; Pais, P.; Parkhomenko, A.; Pedersen, T.R.; Pella, D.; Ramos-Corrales, M.A.; Ruda, M.; Sereg, M.; Siddique, S.; Sinnaeve, P.; Smith, P.; Sritara, P.; Swart, H.P.; Sy, R.G.; Teramoto, T.; Tse, H.F.; Watson, D.; Weaver, W.D.; Weiss, R.; Viigimaa, M.; Vinereanu, D.; Zhu, J.; Cannon, C.P.; Wallentin, L. Darapladib for preventing ischemic events in stable coronary heart disease. N. Engl. J. Med., 2014, 370(18), 1702-1711.
[http://dx.doi.org/10.1056/NEJMoa1315878] [PMID: 24678955]
[98]
O’Donoghue, M.L.; Braunwald, E.; White, H.D.; Lukas, M.A.; Tarka, E.; Steg, P.G.; Hochman, J.S.; Bode, C.; Maggioni, A.P.; Im, K.; Shannon, J.B.; Davies, R.Y.; Murphy, S.A.; Crugnale, S.E.; Wiviott, S.D.; Bonaca, M.P.; Watson, D.F.; Weaver, W.D.; Serruys, P.W.; Cannon, C.P.; Steen, D.L. Effect of darapladib on major coronary events after an acute coronary syndrome: The SOLID-TIMI 52 randomized clinical trial. JAMA, 2014, 312(10), 1006-1015.
[http://dx.doi.org/10.1001/jama.2014.11061] [PMID: 25173516]
[99]
Tardif, J-C.; L’allier, P.L.; Ibrahim, R.; Grégoire, J.C.; Nozza, A.; Cossette, M.; Kouz, S.; Lavoie, M.A.; Paquin, J.; Brotz, T.M.; Taub, R.; Pressacco, J. Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome. Circ. Cardiovasc. Imaging, 2010, 3(3), 298-307.
[http://dx.doi.org/10.1161/CIRCIMAGING.110.937169] [PMID: 20190281]
[100]
Gaztanaga, J.; Farkouh, M.; Rudd, J.H.F.; Brotz, T.M.; Rosenbaum, D.; Mani, V.; Kerwin, T.C.; Taub, R.; Tardif, J.C.; Tawakol, A.; Fayad, Z.A. A phase 2 randomized, double-blind, placebo-controlled study of the effect of VIA-2291, a 5-lipoxygenase inhibitor, on vascular inflammation in patients after an acute coronary syndrome. Atherosclerosis, 2015, 240(1), 53-60.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.02.027] [PMID: 25752438]
[101]
Hakonarson, H.; Thorvaldsson, S.; Helgadottir, A.; Gudbjartsson, D.; Zink, F.; Andresdottir, M.; Manolescu, A.; Arnar, D.O.; Andersen, K.; Sigurdsson, A.; Thorgeirsson, G.; Jonsson, A.; Agnarsson, U.; Bjornsdottir, H.; Gottskalksson, G.; Einarsson, A.; Gudmundsdottir, H.; Adalsteinsdottir, A.E.; Gudmundsson, K.; Kristjansson, K.; Hardarson, T.; Kristinsson, A.; Topol, E.J.; Gulcher, J.; Kong, A.; Gurney, M.; Thorgeirsson, G.; Stefansson, K. Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: A randomized trial. JAMA, 2005, 293(18), 2245-2256.
[http://dx.doi.org/10.1001/jama.293.18.2245] [PMID: 15886380]
[102]
O’Donoghue, M.L.; Glaser, R.; Cavender, M.A.; Aylward, P.E.; Bonaca, M.P.; Budaj, A.; Davies, R.Y.; Dellborg, M.; Fox, K.A.; Gutierrez, J.A.; Hamm, C.; Kiss, R.G.; Kovar, F.; Kuder, J.F.; Im, K.A.; Lepore, J.J.; Lopez-Sendon, J.L.; Ophuis, T.O.; Parkhomenko, A.; Shannon, J.B.; Spinar, J.; Tanguay, J.F.; Ruda, M.; Steg, P.G.; Theroux, P.; Wiviott, S.D.; Laws, I.; Sabatine, M.S.; Morrow, D.A. Effect of losmapimod on cardiovascular outcomes in patients hospitalized with acute myocardial infarction: A randomized clinical trial. JAMA, 2016, 315(15), 1591-1599.
[http://dx.doi.org/10.1001/jama.2016.3609] [PMID: 27043082]
[103]
Newby, L.K.; Marber, M.S.; Melloni, C.; Sarov-Blat, L.; Aberle, L.H.; Aylward, P.E.; Cai, G.; de Winter, R.J.; Hamm, C.W.; Heitner, J.F.; Kim, R.; Lerman, A.; Patel, M.R.; Tanguay, J.F.; Lepore, J.J.; Al-Khalidi, H.R.; Sprecher, D.L.; Granger, C.B. Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: A randomised phase 2 trial. PLoS One, 2018, 13(2), e0191895.
[http://dx.doi.org/10.1016/S0140-6736(14)60417-7] [PMID: 24930728]
[104]
Kawakami, R.; Nozato, Y.; Nakagami, H. Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/kexin type 9 (Pcsk9) epitope in mice. In: PLoS ONE; Vinci, M.C., Ed.; , 2018; 13, p. (2) e0191895.
[http://dx.doi.org/10.1371/journal.pone.0191895]
[105]
Laufs, U.; Ference, B.A. Vaccination to prevent atherosclerotic cardiovascular diseases. Eur. Heart J., 2017, 38(32), 2508-2510.
[http://dx.doi.org/10.1093/eurheartj/ehx302] [PMID: 28637213]
[106]
Lee, K.R.; Bae, J.H.; Hwang, I.C.; Kim, K.K.; Suh, H.S.; Ko, K.D. Effect of influenza vaccination on risk of stroke: A systematic review and meta-analysis. Neuroepidemiology, 2017, 48(3-4), 103-110.
[http://dx.doi.org/10.1159/000478017] [PMID: 28628919]
[107]
Franceschi, C.; Garagnani, P.; Parini, P.; Giuliani, C.; Santoro, A. Inflammaging: A new immune-metabolic viewpoint for age-related diseases. Nat. Rev. Endocrinol., 2018 14 (10), 576-590. http://dx.doi.org/10.1038/s41574- 018-0059-4 PMID: 30046148

Rights & Permissions Print Cite
Article Metrics
22
2
© 2024 Bentham Science Publishers | Privacy Policy