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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Microbiome Medicine: Microbiota in Development and Management of Cardiovascular Diseases

Author(s): Yogesh Garg, Navjot Kanwar, Shruti Chopra, Murtaza M. Tambuwala, Hemraj Dodiya, Amit Bhatia* and Abhinav Kanwal*

Volume 22, Issue 14, 2022

Published on: 02 September, 2022

Page: [1344 - 1356] Pages: 13

DOI: 10.2174/1871530322666220624161712

Price: $65

Abstract

The gut microbiome consists of trillions of bacteria and other microbes whose metabolic activities and interactions with the immune system go beyond the gut itself. We are all aware that bacteria and other microorganisms have a significant impact on our health. Also, the health of the bacteria directly reflects the health status of the body where they reside. Eventually, alterations in the microbiome at different sites of a body are associated with many different diseases such as obesity, IBD, malnutrition, CVD, etc. Microbiota directly or indirectly affects the heart with the formation of plaques in the blood vessels, and cell walls become prone to lesion development. This ultimately leads to heightening the overall inflammatory status via increased bacterial translocation. Metabolites derived from the gut microbial metabolism of choline, phosphatidylcholine, and L-carnitine directly contribute to CVD pathology. These dietary nutrients have trimethylamine (TMA) moiety, which participates in the development of atherosclerotic heart disease. The objective of this review was to examine various metabolic pathways regulated by the gut microbiome that appear to alter heart function and lead to the development and progression of cardiovascular diseases, as well as how to target the gut microbiome for a healthier heart. In this review, we also discussed various clinical drugs having crosstalk between microbiota and heart and clinical trials for the gut-heart microbiome.

Keywords: Gut microbiome, synbiotics, metabolism, cardiovascular disease, heart failure, drugs, gut dysbiosis.

Graphical Abstract

[1]
Wang, J.; Ji, H. Influence of probiotics on dietary protein digestion and utilization in the gastrointestinal tract. Curr. Protein Pept. Sci., 2019, 20(2), 125-131.
[http://dx.doi.org/10.2174/1389203719666180517100339] [PMID: 29769003]
[2]
Lallès, J. Intestinal alkaline phosphatase in the gastrointestinal tract of fish: Biology, ontogeny, and environmental and nutritional modulation. Rev. Aquacult., 2020, 12(2), 555-581.
[http://dx.doi.org/10.1111/raq.12340]
[3]
Davila, A.M.; Blachier, F.; Gotteland, M.; Andriamihaja, M.; Benetti, P.H.; Sanz, Y.; Tomé, D. Re-print of “Intestinal luminal nitrogen metabolism: Role of the gut microbiota and consequences for the host”. Pharmacol. Res., 2013, 69(1), 114-126.
[http://dx.doi.org/10.1016/j.phrs.2013.01.003] [PMID: 23318949]
[4]
Bouter, K.E.; van Raalte, D.H.; Groen, A.K.; Nieuwdorp, M. Role of the gut microbiome in the pathogenesis of obesity and obesity-related metabolic dysfunction. Gastroenterology, 2017, 152(7), 1671-1678.
[http://dx.doi.org/10.1053/j.gastro.2016.12.048] [PMID: 28192102]
[5]
Tlaskalová-Hogenová, H. Stěpánková, R.; Kozáková, H.; Hudcovic, T.; Vannucci, L.; Tučková, L.; Rossmann, P.; Hrnčíř, T.; Kverka, M.; Zákostelská, Z.; Klimešová, K.; Přibylová, J.; Bártová, J.; Sanchez, D.; Fundová, P.; Borovská, D.; Srůtková, D.; Zídek, Z.; Schwarzer, M.; Drastich, P.; Funda, D.P. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: Contribution of germ-free and gnotobiotic animal models of human diseases. Cell. Mol. Immunol., 2011, 8(2), 110-120.
[http://dx.doi.org/10.1038/cmi.2010.67] [PMID: 21278760]
[6]
Verdugo-Meza, A.; Ye, J.; Dadlani, H.; Ghosh, S.; Gibson, D.L. Connecting the dots between inflammatory bowel disease and metabolic syndrome: A focus on gut-derived metabolites. Nutrients, 2020, 12(5), 1434.
[http://dx.doi.org/10.3390/nu12051434] [PMID: 32429195]
[7]
Kau, A.L.; Ahern, P.P.; Griffin, N.W.; Goodman, A.L.; Gordon, J.I. Human nutrition, the gut microbiome and the immune system. Nature, 2011, 474(7351), 327-336.
[http://dx.doi.org/10.1038/nature10213] [PMID: 21677749]
[8]
Goodrich, J.K.; Davenport, E.R.; Clark, A.G.; Ley, R.E. The relationship between the human genome and microbiome comes into view. Annu. Rev. Genet., 2017, 51, 413-433.
[http://dx.doi.org/10.1146/annurev-genet-110711-155532] [PMID: 28934590]
[9]
Jeong, Y.; Kim, J.W.; You, H.J.; Park, S.J.; Lee, J.; Ju, J.H.; Park, M.S.; Jin, H.; Cho, M.L.; Kwon, B.; Park, S.H.; Ji, G.E. Gut microbial composition and function are altered in patients with early rheumatoid arthritis. J. Clin. Med., 2019, 8(5), 693.
[http://dx.doi.org/10.3390/jcm8050693] [PMID: 31100891]
[10]
Sencio, V.; Machado, M.G.; Trottein, F. The lung-gut axis during viral respiratory infections: The impact of gut dysbiosis on secondary disease outcomes. Mucosal Immunol., 2021, 14(2), 296-304.
[http://dx.doi.org/10.1038/s41385-020-00361-8] [PMID: 33500564]
[11]
Carding, S.; Verbeke, K.; Vipond, D.T.; Corfe, B.M.; Owen, L.J. Dysbiosis of the gut microbiota in disease. Microb. Ecol. Health Dis., 2015, 26(1), 26191.
[PMID: 25651997]
[12]
Singh, R.K.; Chang, H.W.; Yan, D.; Lee, K.M.; Ucmak, D.; Wong, K.; Abrouk, M.; Farahnik, B.; Nakamura, M.; Zhu, T.H.; Bhutani, T.; Liao, W. Influence of diet on the gut microbiome and implications for human health. J. Transl. Med., 2017, 15(1), 73.
[http://dx.doi.org/10.1186/s12967-017-1175-y] [PMID: 28388917]
[13]
Tang, W.H.W.; Kitai, T.; Hazen, S.L. Gut microbiota in cardiovascular health and disease. Circ. Res., 2017, 120(7), 1183-1196.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.309715] [PMID: 28360349]
[14]
Savarese, G.; Lund, L.H. Global public health burden of heart failure. Card. Fail. Rev., 2017, 3(1), 7-11.
[http://dx.doi.org/10.15420/cfr.2016:25:2] [PMID: 28785469]
[15]
World Health Organisation Cardiovasc. Dis., 2017. Available from: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
[16]
Velasquez, M.T.; Centron, P.; Barrows, I.; Dwivedi, R.; Raj, D.S. Gut microbiota and cardiovascular uremic toxicities. Toxins (Basel), 2018, 10(7), 287.
[http://dx.doi.org/10.3390/toxins10070287] [PMID: 29997362]
[17]
Ahmad, A.F.; Ward, N.C.; Dwivedi, G. The gut microbiome and heart failure. Curr. Opin. Cardiol., 2019, 34(2), 225-232.
[http://dx.doi.org/10.1097/HCO.0000000000000598] [PMID: 30575647]
[18]
Sekirov, I.; Russell, S.L.; Antunes, L.C.M.; Finlay, B.B. Gut microbiota in health and disease. Physiol. Rev., 2010, 90(3), 859-904.
[http://dx.doi.org/10.1152/physrev.00045.2009] [PMID: 20664075]
[19]
Camilleri, M.; Lyle, B.J.; Madsen, K.L.; Sonnenburg, J.; Verbeke, K.; Wu, G.D. Role for diet in normal gut barrier function: Developing guidance within the framework of food-labeling regulations. Am. J. Physiol. Gastrointest. Liver Physiol., 2019, 317(1), G17-G39.
[http://dx.doi.org/10.1152/ajpgi.00063.2019] [PMID: 31125257]
[20]
Sircana, A.; De Michieli, F.; Parente, R.; Framarin, L.; Leone, N.; Berrutti, M.; Paschetta, E.; Bongiovanni, D.; Musso, G. Gut microbiota, hypertension and chronic kidney disease: Recent advances. Pharmacol. Res., 2019, 144, 390-408.
[http://dx.doi.org/10.1016/j.phrs.2018.01.013] [PMID: 29378252]
[21]
Khosravi, A.; Yáñez, A.; Price, J.G.; Chow, A.; Merad, M.; Goodridge, H.S.; Mazmanian, S.K. Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe, 2014, 15(3), 374-381.
[http://dx.doi.org/10.1016/j.chom.2014.02.006] [PMID: 24629343]
[22]
Belizário, J.E.; Faintuch, J. Microbiome and gut dysbiosis. In: Silvestre, R.; Torrado, E.; Eds. Metabolic Interaction in Infection, Springer: Cham, 2018, pp. 459-476
[http://dx.doi.org/10.1007/978-3-319-74932-7_13]
[23]
Sandek, A.; Bauditz, J.; Swidsinski, A.; Buhner, S.; Weber-Eibel, J.; von Haehling, S.; Schroedl, W.; Karhausen, T.; Doehner, W.; Rauchhaus, M.; Poole-Wilson, P.; Volk, H.D.; Lochs, H.; Anker, S.D. Altered intestinal function in patients with chronic heart failure. J. Am. Coll. Cardiol., 2007, 50(16), 1561-1569.
[http://dx.doi.org/10.1016/j.jacc.2007.07.016] [PMID: 17936155]
[24]
Sandek, A.; Haehling, S.D.A. von, S The gut and intestinal bacteria in chronic heart failure. Current Drug Metabolism, 2009, 10, 22-28.
[25]
Charlet, R.; Bortolus, C.; Barbet, M.; Sendid, B.; Jawhara, S. A decrease in anaerobic bacteria promotes Candida glabrata overgrowth while β-glucan treatment restores the gut microbiota and attenuates colitis. Gut Pathog., 2018, 10(1), 50.
[http://dx.doi.org/10.1186/s13099-018-0277-2] [PMID: 30524506]
[26]
Yu, M.; Jia, H.; Zhou, C.; Yang, Y.; Zhao, Y.; Yang, M.; Zou, Z. Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC/MS-based metabolomics. J. Pharm. Biomed. Anal., 2017, 138, 231-239.
[http://dx.doi.org/10.1016/j.jpba.2017.02.008] [PMID: 28219800]
[27]
Kamo, T.; Akazawa, H.; Suda, W.; Saga-Kamo, A.; Shimizu, Y.; Yagi, H.; Liu, Q.; Nomura, S.; Naito, A.T.; Takeda, N.; Harada, M.; Toko, H.; Kumagai, H.; Ikeda, Y.; Takimoto, E.; Suzuki, J.I.; Honda, K.; Morita, H.; Hattori, M.; Komuro, I. Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure. PLoS One, 2017, 12(3), e0174099.
[http://dx.doi.org/10.1371/journal.pone.0174099] [PMID: 28328981]
[28]
Tang, W.H.W.; Wang, Z.; Levison, B.S.; Koeth, R.A.; Britt, E.B.; Fu, X.; Wu, Y.; Hazen, S.L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med., 2013, 368(17), 1575-1584.
[http://dx.doi.org/10.1056/NEJMoa1109400] [PMID: 23614584]
[29]
Tang, W.H.W.; Wang, Z.; Fan, Y.; Levison, B.; Hazen, J.E.; Donahue, L.M.; Wu, Y.; Hazen, S.L. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: Refining the gut hypothesis. J. Am. Coll. Cardiol., 2014, 64(18), 1908-1914.
[http://dx.doi.org/10.1016/j.jacc.2014.02.617] [PMID: 25444145]
[30]
Shimokawa, H.; Miura, M.; Nochioka, K.; Sakata, Y. Heart failure as a general pandemic in Asia. Eur. J. Heart Fail., 2015, 17(9), 884-892.
[http://dx.doi.org/10.1002/ejhf.319] [PMID: 26222508]
[31]
Karlsson, F.H.; Fåk, F.; Nookaew, I.; Tremaroli, V.; Fagerberg, B.; Petranovic, D.; Bäckhed, F.; Nielsen, J. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat. Commun., 2012, 3, 1245.
[http://dx.doi.org/10.1038/ncomms2266] [PMID: 23212374]
[32]
Emoto, T.; Yamashita, T.; Sasaki, N.; Hirota, Y.; Hayashi, T.; So, A.; Kasahara, K.; Yodoi, K.; Matsumoto, T.; Mizoguchi, T.; Ogawa, W.; Hirata, K. Analysis of gut microbiota in coronary artery disease patients: A possible link between gut microbiota and coronary artery disease. J. Atheroscler. Thromb., 2016, 23(8), 908-921.
[http://dx.doi.org/10.5551/jat.32672] [PMID: 26947598]
[33]
Jie, Z.; Xia, H.; Zhong, S.L.; Feng, Q.; Li, S.; Liang, S.; Zhong, H.; Liu, Z.; Gao, Y.; Zhao, H.; Zhang, D.; Su, Z.; Fang, Z.; Lan, Z.; Li, J.; Xiao, L.; Li, J.; Li, R.; Li, X.; Li, F.; Ren, H.; Huang, Y.; Peng, Y.; Li, G.; Wen, B.; Dong, B.; Chen, J.Y.; Geng, Q.S.; Zhang, Z.W.; Yang, H.; Wang, J.; Wang, J.; Zhang, X.; Madsen, L.; Brix, S.; Ning, G.; Xu, X.; Liu, X.; Hou, Y.; Jia, H.; He, K.; Kristiansen, K. The gut microbiome in atherosclerotic cardiovascular disease. Nat. Commun., 2017, 8(1), 845.
[http://dx.doi.org/10.1038/s41467-017-00900-1] [PMID: 29018189]
[34]
Fåk, F.; Tremaroli, V.; Bergström, G.; Bäckhed, F. Oral microbiota in patients with atherosclerosis. Atherosclerosis, 2015, 243(2), 573-578.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.10.097] [PMID: 26536303]
[35]
Lv, L.X.; Fang, D.Q.; Shi, D.; Chen, D.Y.; Yan, R.; Zhu, Y.X.; Chen, Y.F.; Shao, L.; Guo, F.F.; Wu, W.R.; Li, A.; Shi, H.Y.; Jiang, X.W.; Jiang, H.Y.; Xiao, Y.H.; Zheng, S.S.; Li, L.J. Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis. Environ. Microbiol., 2016, 18(7), 2272-2286.
[http://dx.doi.org/10.1111/1462-2920.13401] [PMID: 27243236]
[36]
Jonsson, A.L.; Bäckhed, F. Role of gut microbiota in atherosclerosis. Nat. Rev. Cardiol., 2017, 14(2), 79-87.
[http://dx.doi.org/10.1038/nrcardio.2016.183] [PMID: 27905479]
[37]
Priyamvara, A.; Dey, A.K.; Bandyopadhyay, D.; Katikineni, V.; Zaghlol, R.; Basyal, B.; Barssoum, K.; Amarin, R.; Bhatt, D.L.; Lavie, C.J. Periodontal inflammation and the risk of cardiovascular disease. Curr. Atheroscler. Rep., 2020, 22(7), 28.
[http://dx.doi.org/10.1007/s11883-020-00848-6] [PMID: 32514778]
[38]
Astbury, S.; Atallah, E.; Vijay, A.; Aithal, G.P.; Grove, J.I.; Valdes, A.M. Lower gut microbiome diversity and higher abundance of proinflammatory genus Collinsella are associated with biopsy-proven nonalcoholic steatohepatitis. Gut Microbes, 2020, 11(3), 569-580.
[http://dx.doi.org/10.1080/19490976.2019.1681861] [PMID: 31696774]
[39]
Rinninella, E.; Raoul, P.; Cintoni, M.; Franceschi, F.; Miggiano, G.A.D.; Gasbarrini, A.; Mele, M.C. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms, 2019, 7(1), 14.
[http://dx.doi.org/10.3390/microorganisms7010014] [PMID: 30634578]
[40]
Amabebe, E.; Robert, F.O.; Agbalalah, T.; Orubu, E.S.F. Microbial dysbiosis-induced obesity: Role of gut microbiota in homoeostasis of energy metabolism. Br. J. Nutr., 2020, 123(10), 1127-1137.
[http://dx.doi.org/10.1017/S0007114520000380] [PMID: 32008579]
[41]
Cox, A.J.; West, N.P.; Cripps, A.W. Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol., 2015, 3(3), 207-215.
[http://dx.doi.org/10.1016/S2213-8587(14)70134-2] [PMID: 25066177]
[42]
Tilg, H.; Zmora, N.; Adolph, T.E.; Elinav, E. The intestinal microbiota fuelling metabolic inflammation. Nat. Rev. Immunol., 2020, 20(1), 40-54.
[http://dx.doi.org/10.1038/s41577-019-0198-4] [PMID: 31388093]
[43]
Komaroff, A.L. The microbiome and risk for atherosclerosis. JAMA, 2018, 319(23), 2381-2382.
[http://dx.doi.org/10.1001/jama.2018.5240] [PMID: 29800043]
[44]
Zinöcker, M.K.; Lindseth, I.A. The Western diet–microbiome-host interaction and its role in metabolic disease. Nutrients, 2018, 10(3), 365.
[http://dx.doi.org/10.3390/nu10030365] [PMID: 29562591]
[45]
De Filippis, F.; Pellegrini, N.; Vannini, L.; Jeffery, I.B.; La Storia, A.; Laghi, L.; Serrazanetti, D.I.; Di Cagno, R.; Ferrocino, I.; Lazzi, C.; Turroni, S.; Cocolin, L.; Brigidi, P.; Neviani, E.; Gobbetti, M.; O’Toole, P.W.; Ercolini, D. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut, 2016, 65(11), 1812-1821.
[http://dx.doi.org/10.1136/gutjnl-2015-309957] [PMID: 26416813]
[46]
Morera, L.P.; Marchiori, G.N.; Medrano, L.A.; Defagó, M.D. Stress, dietary patterns and cardiovascular disease: A mini-review. Front. Neurosci., 2019, 13, 1226.
[http://dx.doi.org/10.3389/fnins.2019.01226] [PMID: 31780892]
[47]
Laugerette, F.; Furet, J.P.; Debard, C.; Daira, P.; Loizon, E.; Géloën, A.; Soulage, C.O.; Simonet, C.; Lefils-Lacourtablaise, J.; Bernoud-Hubac, N.; Bodennec, J.; Peretti, N.; Vidal, H.; Michalski, M.C. Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors in mice. Am. J. Physiol. Endocrinol. Metab., 2012, 302(3), E374-E386.
[http://dx.doi.org/10.1152/ajpendo.00314.2011] [PMID: 22094473]
[48]
Forkosh, E.; Ilan, Y. The heart-gut axis: New target for atherosclerosis and congestive heart failure therapy. Open Heart, 2019, 6(1), e000993.
[http://dx.doi.org/10.1136/openhrt-2018-000993] [PMID: 31168383]
[49]
Tang, W.H.W.; Bäckhed, F.; Landmesser, U.; Hazen, S.L. Intestinal microbiota in cardiovascular health and disease: JACC state-of-the-art review. J. Am. Coll. Cardiol., 2019, 73(16), 2089-2105.
[http://dx.doi.org/10.1016/j.jacc.2019.03.024] [PMID: 31023434]
[50]
Scarmozzino, F.; Poli, A.; Visioli, F. Microbiota and cardiovascular disease risk: A scoping review. Pharmacol. Res., 2020, 159, 104952.
[http://dx.doi.org/10.1016/j.phrs.2020.104952] [PMID: 32492487]
[51]
Tang, W.H.W.; Hazen, S.L. The contributory role of gut microbiota in cardiovascular disease. J. Clin. Invest., 2014, 124(10), 4204-4211.
[http://dx.doi.org/10.1172/JCI72331] [PMID: 25271725]
[52]
Roberts, A.B.; Gu, X.; Buffa, J.A.; Hurd, A.G.; Wang, Z.; Zhu, W.; Gupta, N.; Skye, S.M.; Cody, D.B.; Levison, B.S.; Barrington, W.T.; Russell, M.W.; Reed, J.M.; Duzan, A.; Lang, J.M.; Fu, X.; Li, L.; Myers, A.J.; Rachakonda, S.; DiDonato, J.A.; Brown, J.M.; Gogonea, V.; Lusis, A.J.; Garcia-Garcia, J.C.; Hazen, S.L. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat. Med., 2018, 24(9), 1407-1417.
[http://dx.doi.org/10.1038/s41591-018-0128-1] [PMID: 30082863]
[53]
Wang, Z.; Bergeron, N.; Levison, B.S.; Li, X.S.; Chiu, S.; Jia, X.; Koeth, R.A.; Li, L.; Wu, Y.; Tang, W.H.W.; Krauss, R.M.; Hazen, S.L. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur. Heart J., 2019, 40(7), 583-594.
[http://dx.doi.org/10.1093/eurheartj/ehy799] [PMID: 30535398]
[54]
Chen, X.; Li, H.Y.; Hu, X.M.; Zhang, Y.; Zhang, S.Y. Current understanding of gut microbiota alterations and related therapeutic intervention strategies in heart failure. Chin. Med. J. (Engl.), 2019, 132(15), 1843-1855.
[http://dx.doi.org/10.1097/CM9.0000000000000330] [PMID: 31306229]
[55]
Zeisel, S.H.; Warrier, M. Trimethylamine N-oxide, the microbiome, and heart and kidney disease. Annu. Rev. Nutr., 2017, 37, 157-181.
[http://dx.doi.org/10.1146/annurev-nutr-071816-064732] [PMID: 28715991]
[56]
Canyelles, M.; Tondo, M.; Cedó, L.; Farràs, M.; Escolà-Gil, J.C.; Blanco-Vaca, F. Trimethylamine N-oxide: A link among diet, gut microbiota, gene regulation of liver and intestine cholesterol homeostasis and HDL function. Int. J. Mol. Sci., 2018, 19(10), 3228.
[http://dx.doi.org/10.3390/ijms19103228] [PMID: 30347638]
[57]
Van Parys, A.; Lysne, V.; Øyen, J.; Dierkes, J.; Nygård, O. No effect of plasma trimethylamine N-Oxide (TMAO) and plasma trimethyllysine (TML) on the association between choline intake and acute myocardial infarction risk in patients with stable angina pectoris. Human Nutr. Metabol., 2020, 21, 200112.
[http://dx.doi.org/10.1016/j.hnm.2020.200112]
[58]
Tang, W.H.W.; Hazen, S.L. Microbiome, trimethylamine N-oxide, and cardiometabolic disease. Transl. Res., 2017, 179, 108-115.
[http://dx.doi.org/10.1016/j.trsl.2016.07.007] [PMID: 27490453]
[59]
Nowiński, A.; Ufnal, M. Trimethylamine N-oxide: A harmful, protective or diagnostic marker in lifestyle diseases? Nutrition, 2018, 46, 7-12.
[http://dx.doi.org/10.1016/j.nut.2017.08.001] [PMID: 29290360]
[60]
Trøseid, M.; Ueland, T.; Hov, J.R.; Svardal, A.; Gregersen, I.; Dahl, C.P.; Aakhus, S.; Gude, E.; Bjørndal, B.; Halvorsen, B.; Karlsen, T.H.; Aukrust, P.; Gullestad, L.; Berge, R.K.; Yndestad, A. Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J. Intern. Med., 2015, 277(6), 717-726.
[http://dx.doi.org/10.1111/joim.12328] [PMID: 25382824]
[61]
Bach Knudsen, K.E.; Lærke, H.N.; Hedemann, M.S.; Nielsen, T.S.; Ingerslev, A.K.; Gundelund Nielsen, D.S.; Theil, P.K.; Purup, S.; Hald, S.; Schioldan, A.G.; Marco, M.L.; Gregersen, S.; Hermansen, K. Impact of diet-modulated butyrate production on intestinal barrier function and inflammation. Nutrients, 2018, 10(10), 1499.
[http://dx.doi.org/10.3390/nu10101499] [PMID: 30322146]
[62]
Parada Venegas, D.; De la Fuente, M.K.; Landskron, G.; González, M.J.; Quera, R.; Dijkstra, G.; Harmsen, H.J.M.; Faber, K.N.; Hermoso, M.A. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front. Immunol., 2019, 10, 277.
[http://dx.doi.org/10.3389/fimmu.2019.00277] [PMID: 30915065]
[63]
Chen, J.; Vitetta, L. The role of butyrate in attenuating pathobiont-induced hyperinflammation. Immune Netw., 2020, 20(2), e15.
[http://dx.doi.org/10.4110/in.2020.20.e15] [PMID: 32395367]
[64]
Bischoff, S.C.; Barbara, G.; Buurman, W.; Ockhuizen, T.; Schulzke, J.D.; Serino, M.; Tilg, H.; Watson, A.; Wells, J.M. Intestinal permeability--a new target for disease prevention and therapy. BMC Gastroenterol., 2014, 14(1), 189.
[http://dx.doi.org/10.1186/s12876-014-0189-7] [PMID: 25407511]
[65]
Trøseid, M.; Andersen, G.Ø.; Broch, K.; Hov, J.R. The gut microbiome in coronary artery disease and heart failure: Current knowledge and future directions. EBioMedicine, 2020, 52, 102649.
[http://dx.doi.org/10.1016/j.ebiom.2020.102649] [PMID: 32062353]
[66]
Yoo, J.Y.; Groer, M.; Dutra, S.V.O.; Sarkar, A.; McSkimming, D.I. Gut microbiota and immune system interactions. Microorganisms, 2020, 8(10), 1587.
[http://dx.doi.org/10.3390/microorganisms8101587] [PMID: 33076307]
[67]
Fang, W.; Xue, H.; Chen, X.; Chen, K.; Ling, W. Supplementation with sodium butyrate modulates the composition of the gut microbiota and ameliorates high-fat diet-induced obesity in mice. J. Nutr., 2019, 149(5), 747-754.
[http://dx.doi.org/10.1093/jn/nxy324] [PMID: 31004166]
[68]
Mafra, D.; Lobo, J.C.; Barros, A.F.; Koppe, L.; Vaziri, N.D.; Fouque, D. Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol., 2014, 9(3), 399-410.
[http://dx.doi.org/10.2217/fmb.13.165] [PMID: 24762311]
[69]
Mirzaeian, S.; Saraf-Bank, S.; Entezari, M.H.; Hekmatdoost, A.; Feizi, A.; Atapour, A. Effects of synbiotic supplementation on microbiota-derived protein-bound uremic toxins, systemic inflammation, and biochemical parameters in patients on hemodialysis: A double-blind, placebo-controlled, randomized clinical trial. Nutrition, 2020, 73, 110713.
[http://dx.doi.org/10.1016/j.nut.2019.110713] [PMID: 32120316]
[70]
Filipska, I.; Winiarska, A.; Knysak, M.; Stompór, T. Contribution of gut microbiota-derived uremic toxins to the cardiovascular system mineralization. Toxins (Basel), 2021, 13(4), 274.
[http://dx.doi.org/10.3390/toxins13040274] [PMID: 33920096]
[71]
Sallée, M.; Dou, L.; Cerini, C.; Poitevin, S.; Brunet, P.; Burtey, S. The aryl hydrocarbon receptor-activating effect of uremic toxins from tryptophan metabolism: A new concept to understand cardiovascular complications of chronic kidney disease. Toxins (Basel), 2014, 6(3), 934-949.
[http://dx.doi.org/10.3390/toxins6030934] [PMID: 24599232]
[72]
Lekawanvijit, S. Cardiotoxicity of uremic toxins: A driver of cardiorenal syndrome. Toxins (Basel), 2018, 10(9), 352.
[http://dx.doi.org/10.3390/toxins10090352] [PMID: 30200452]
[73]
Mishra, A.K.; Dubey, V.; Ghosh, A.R. Obesity: An overview of possible role(s) of gut hormones, lipid sensing and gut microbiota. Metabolism, 2016, 65(1), 48-65.
[http://dx.doi.org/10.1016/j.metabol.2015.10.008] [PMID: 26683796]
[74]
Chambers, E.S.; Preston, T.; Frost, G.; Morrison, D.J. Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health. Curr. Nutr. Rep., 2018, 7(4), 198-206.
[http://dx.doi.org/10.1007/s13668-018-0248-8] [PMID: 30264354]
[75]
Sente, T.; Van Berendoncks, A.M.; Hoymans, V.Y.; Vrints, C.J. Adiponectin resistance in skeletal muscle: pathophysiological implications in chronic heart failure. J. Cachexia Sarcopenia Muscle, 2016, 7(3), 261-274.
[http://dx.doi.org/10.1002/jcsm.12086] [PMID: 27239409]
[76]
Wang, Y.; Ma, X.L.; Lau, W.B. Cardiovascular adiponectin resistance: The critical role of adiponectin receptor modification. Trends Endocrinol. Metab., 2017, 28(7), 519-530.
[http://dx.doi.org/10.1016/j.tem.2017.03.004] [PMID: 28473178]
[77]
Luedde, M.; Winkler, T.; Heinsen, F.A.; Rühlemann, M.C.; Spehlmann, M.E.; Bajrovic, A.; Lieb, W.; Franke, A.; Ott, S.J.; Frey, N. Heart failure is associated with depletion of core intestinal microbiota. ESC Heart Fail., 2017, 4(3), 282-290.
[http://dx.doi.org/10.1002/ehf2.12155] [PMID: 28772054]
[78]
Cui, X.; Ye, L.; Li, J.; Jin, L.; Wang, W.; Li, S.; Bao, M.; Wu, S.; Li, L.; Geng, B.; Zhou, X.; Zhang, J.; Cai, J. Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients. Sci. Rep., 2018, 8(1), 635.
[http://dx.doi.org/10.1038/s41598-017-18756-2] [PMID: 29330424]
[79]
Pasini, E.; Aquilani, R.; Testa, C.; Baiardi, P.; Angioletti, S.; Boschi, F.; Verri, M.; Dioguardi, F. Pathogenic gut flora in patients with chronic heart failure. JACC Heart Fail., 2016, 4(3), 220-227.
[http://dx.doi.org/10.1016/j.jchf.2015.10.009] [PMID: 26682791]
[80]
Luedde, M.; Spehlmann, M.E.; Frey, N. Progress in heart failure treatment in Germany. Clin. Res. Cardiol., 2018, 107(2)(Suppl. 2), 105-113.
[http://dx.doi.org/10.1007/s00392-018-1317-0] [PMID: 29968196]
[81]
Sánchez, B.; Delgado, S.; Blanco-Míguez, A.; Lourenço, A.; Gueimonde, M.; Margolles, A. Probiotics, gut microbiota, and their influence on host health and disease. Mol. Nutr. Food Res., 2017, 61(1), 1600240.
[http://dx.doi.org/10.1002/mnfr.201600240] [PMID: 27500859]
[82]
Martín, R.; Langella, P. Emerging health concepts in the probiotics field: Streamlining the definitions. Front. Microbiol., 2019, 10, 1047.
[http://dx.doi.org/10.3389/fmicb.2019.01047] [PMID: 31164874]
[83]
Kothari, D.; Patel, S.; Kim, S.K. Probiotic supplements might not be universally-effective and safe: A review. Biomed. Pharmacother., 2019, 111, 537-547.
[http://dx.doi.org/10.1016/j.biopha.2018.12.104] [PMID: 30597307]
[84]
Voidarou, C. Antoniadou, Μ; Rozos, G.; Tzora, A.; Skoufos, I.; Varzakas, T.; Lagiou, A.; Bezirtzoglou, E. Fermentative foods: Microbiology, biochemistry, potential human health benefits and public health issues. Foods, 2020, 10(1), 69.
[http://dx.doi.org/10.3390/foods10010069] [PMID: 33396397]
[85]
Solas, M.; Milagro, F.I.; Ramírez, M.J.; Martínez, J.A. Inflammation and gut-brain axis link obesity to cognitive dysfunction: Plausible pharmacological interventions. Curr. Opin. Pharmacol., 2017, 37, 87-92.
[http://dx.doi.org/10.1016/j.coph.2017.10.005] [PMID: 29107872]
[86]
Oniszczuk, A.; Oniszczuk, T.; Gancarz, M. Szymańska, J. Role of gut microbiota, probiotics and prebiotics in the cardiovascular diseases. Molecules, 2021, 26(4), 1172.
[http://dx.doi.org/10.3390/molecules26041172] [PMID: 33671813]
[87]
Kleerebezem, M.; Vaughan, E.E. Probiotic and gut lactobacilli and bifidobacteria: Molecular approaches to study diversity and activity. Annu. Rev. Microbiol., 2009, 63, 269-290.
[http://dx.doi.org/10.1146/annurev.micro.091208.073341] [PMID: 19575569]
[88]
Sekhon, B.S.; Jairath, S. Prebiotics, probiotics and synbiotics: An overview. J. Pharm. Edu. Res., 2010, 1(2), 13-36.
[89]
Markowiak, P. Śliżewska, K. The role of probiotics, prebiotics and synbiotics in animal nutrition. Gut Pathog., 2018, 10(1), 21.
[http://dx.doi.org/10.1186/s13099-018-0250-0] [PMID: 29930711]
[90]
Sanders, M.E.; Merenstein, D.J.; Reid, G.; Gibson, G.R.; Rastall, R.A. Probiotics and prebiotics in intestinal health and disease: From biology to the clinic. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(10), 605-616.
[http://dx.doi.org/10.1038/s41575-019-0173-3] [PMID: 31296969]
[91]
Liu, Y.; Alookaran, J.J.; Rhoads, J.M. Probiotics in autoimmune and inflammatory disorders. Nutrients, 2018, 10(10), 1537.
[http://dx.doi.org/10.3390/nu10101537] [PMID: 30340338]
[92]
Moludi, J.; Alizadeh, M.; Davari, M.; Golmohammadi, A.; Maleki, V. The efficacy and safety of probiotics intervention in attenuating cardiac remodeling following myocardial infraction: Literature review and study protocol for a randomized, double-blinded, placebo controlled trial. Contemp. Clin. Trials Commun., 2019, 15, 100364.
[http://dx.doi.org/10.1016/j.conctc.2019.100364] [PMID: 31193187]
[93]
Gan, X.T.; Ettinger, G.; Huang, C.X.; Burton, J.P.; Haist, J.V.; Rajapurohitam, V.; Sidaway, J.E.; Martin, G.; Gloor, G.B.; Swann, J.R.; Reid, G.; Karmazyn, M. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ. Heart Fail., 2014, 7(3), 491-499.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.113.000978] [PMID: 24625365]
[94]
Lam, V.; Su, J.; Koprowski, S.; Hsu, A.; Tweddell, J.S.; Rafiee, P.; Gross, G.J.; Salzman, N.H.; Baker, J.E. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J., 2012, 26(4), 1727-1735.
[http://dx.doi.org/10.1096/fj.11-197921] [PMID: 22247331]
[95]
Costanza, A.C.; Moscavitch, S.D.; Faria Neto, H.C.C.; Mesquita, E.T. Probiotic therapy with Saccharomyces boulardii for heart failure patients: A randomized, double-blind, placebo-controlled pilot trial. Int. J. Cardiol., 2015, 179, 348-350.
[http://dx.doi.org/10.1016/j.ijcard.2014.11.034]
[96]
Gómez-Guzmán, M.; Toral, M.; Romero, M.; Jiménez, R.; Galindo, P.; Sánchez, M.; Zarzuelo, M.J.; Olivares, M.; Gálvez, J.; Duarte, J. Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol. Nutr. Food Res., 2015, 59(11), 2326-2336.
[http://dx.doi.org/10.1002/mnfr.201500290] [PMID: 26255877]
[97]
Sarkar, D.; Ankolekar, C.; Shetty, K. Functional food components for preventing and combating type 2 diabetes. In: Patil, B.S.; Jayaprakasha, G.K.; Murthy, K.N.C.; Seeram, N.P.; Eds. Emerging Trends in Dietary Components for Preventing and Combating Disease., ACS Publications: Wasgington DC, 2012, pp. 345-374.
[http://dx.doi.org/10.1021/bk-2012-1093.ch020]
[98]
Saad, B.; Zaid, H.; Shanak, S.; Kadan, S. Anti-Diabetes and Anti-Obesity Medicinal Plants and Phytochemicals; Springer Cham, 2017.
[http://dx.doi.org/10.1007/978-3-319-54102-0]
[99]
De Sousa, V.M.C.; Dos Santos, E.V.; Sgarbieri, V.C. The importance of prebiotics in functional foods and clinical practice. Food Nutr. Sci., 2011, 2(2)
[100]
George Kerry, R.; Patra, J.K.; Gouda, S.; Park, Y.; Shin, H.S.; Das, G. Benefaction of probiotics for human health: A review. J. Food Drug Anal., 2018, 26(3), 927-939.
[http://dx.doi.org/10.1016/j.jfda.2018.01.002] [PMID: 29976412]
[101]
Macfarlane, G.T.; Macfarlane, S. Fermentation in the human large intestine: Its physiologic consequences and the potential contribution of prebiotics. J. Clin. Gastroenterol., 2011, 45(Suppl.), S120-S127.
[http://dx.doi.org/10.1097/MCG.0b013e31822fecfe] [PMID: 21992950]
[102]
Ashaolu, T.J.; Ashaolu, J.O.; Adeyeye, S.A.O. Fermentation of prebiotics by human colonic microbiota in vitro and short-chain fatty acids production: A critical review. J. Appl. Microbiol., 2021, 130(3), 677-687.
[http://dx.doi.org/10.1111/jam.14843] [PMID: 32892434]
[103]
Damaskos, D.; Kolios, G. Probiotics and prebiotics in inflammatory bowel disease: Microflora ‘on the scope’. Br. J. Clin. Pharmacol., 2008, 65(4), 453-467.
[http://dx.doi.org/10.1111/j.1365-2125.2008.03096.x] [PMID: 18279467]
[104]
Mohanty, D.; Misra, S.; Mohapatra, S.; Sahu, P.S. Prebiotics and synbiotics: Recent concepts in nutrition. Food Biosci., 2018, 26, 152-160.
[http://dx.doi.org/10.1016/j.fbio.2018.10.008]
[105]
Palai, S.; Derecho, C.M.P.; Kesh, S.S.; Egbuna, C.; Onyeike, P.C. Prebiotics, probiotics, synbiotics and its importance in the management of diseases. In: Egbuna, C.; Dable Tupas, G.; Eds. Functional Foods and Nutraceuticals., Springer Cham,. 2020, 173-196.
[http://dx.doi.org/10.1007/978-3-030-42319-3_10]
[106]
Marques, F.Z.; Nelson, E.; Chu, P.Y.; Horlock, D.; Fiedler, A.; Ziemann, M.; Tan, J.K.; Kuruppu, S.; Rajapakse, N.W.; El-Osta, A.; Mackay, C.R.; Kaye, D.M. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation, 2017, 135(10), 964-977.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024545] [PMID: 27927713]
[107]
Patel, B.; Kumar, P.; Banerjee, R.; Basu, M.; Pal, A.; Samanta, M.; Das, S. Lactobacillus acidophilus attenuates Aeromonas hydrophila induced cytotoxicity in catla thymus macrophages by modulating oxidative stress and inflammation. Mol. Immunol., 2016, 75, 69-83.
[http://dx.doi.org/10.1016/j.molimm.2016.05.012] [PMID: 27262084]
[108]
Guarino, M.P.L.; Altomare, A.; Emerenziani, S.; Di Rosa, C.; Ribolsi, M.; Balestrieri, P.; Iovino, P.; Rocchi, G.; Cicala, M. Mechanisms of action of prebiotics and their effects on gastro-intestinal disorders in adults. Nutrients, 2020, 12(4), 1037.
[http://dx.doi.org/10.3390/nu12041037] [PMID: 32283802]
[109]
Netto, B.D.M.; Bettini, S.C.; Clemente, A.P.G.; Ferreira, J.P.; Boritza, K. Souza, Sde.F.; Von der Heyde, M.E.; Earthman, C.P.; Dâmaso, A.R. Roux-en-Y gastric bypass decreases pro-inflammatory and thrombotic biomarkers in individuals with extreme obesity. Obes. Surg., 2015, 25(6), 1010-1018.
[http://dx.doi.org/10.1007/s11695-014-1484-7] [PMID: 25403776]
[110]
Ashrafian, H.; Li, J.V.; Spagou, K.; Harling, L.; Masson, P.; Darzi, A.; Nicholson, J.K.; Holmes, E.; Athanasiou, T. Bariatric surgery modulates circulating and cardiac metabolites. J. Proteome Res., 2014, 13(2), 570-580.
[http://dx.doi.org/10.1021/pr400748f] [PMID: 24279706]
[111]
Wang, Y.H. Current progress of research on intestinal bacterial translocation. Microb. Pathog., 2021, 152, 104652.
[http://dx.doi.org/10.1016/j.micpath.2020.104652] [PMID: 33249165]
[112]
Li, J.; Lin, S.; Vanhoutte, P.M.; Woo, C.W.; Xu, A. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe-/- Mice. Circulation, 2016, 133(24), 2434-2446.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.019645] [PMID: 27143680]
[113]
Branchereau, M.; Burcelin, R.; Heymes, C. The gut microbiome and heart failure: A better gut for a better heart. Rev. Endocr. Metab. Disord., 2019, 20(4), 407-414.
[http://dx.doi.org/10.1007/s11154-019-09519-7] [PMID: 31705258]
[114]
Pamer, E.G. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science, 2016, 352(6285), 535-538.
[http://dx.doi.org/10.1126/science.aad9382]
[115]
Du, Y.; Li, X.; Su, C.; Wang, L.; Jiang, J.; Hong, B. The human gut microbiome - a new and exciting avenue in cardiovascular drug discovery. Expert Opin. Drug Discov., 2019, 14(10), 1037-1052.
[http://dx.doi.org/10.1080/17460441.2019.1638909] [PMID: 31315489]
[116]
Wang, Z.; Roberts, A.B.; Buffa, J.A.; Levison, B.S.; Zhu, W.; Org, E.; Gu, X.; Huang, Y.; Zamanian-Daryoush, M.; Culley, M.K.; DiDonato, A.J.; Fu, X.; Hazen, J.E.; Krajcik, D.; DiDonato, J.A.; Lusis, A.J.; Hazen, S.L. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell, 2015, 163(7), 1585-1595.
[http://dx.doi.org/10.1016/j.cell.2015.11.055] [PMID: 26687352]
[117]
Singh, V.; Yeoh, B.S.; Vijay-Kumar, M. Gut microbiome as a novel cardiovascular therapeutic target. Curr. Opin. Pharmacol., 2016, 27, 8-12.
[http://dx.doi.org/10.1016/j.coph.2016.01.002] [PMID: 26828626]
[118]
de Groot, P.F.; Frissen, M.N.; de Clercq, N.C.; Nieuwdorp, M. Fecal microbiota transplantation in metabolic syndrome: History, present and future. Gut Microbes, 2017, 8(3), 253-267.
[http://dx.doi.org/10.1080/19490976.2017.1293224] [PMID: 28609252]
[119]
Vrieze, A.; Van Nood, E.; Holleman, F.; Salojärvi, J.; Kootte, R.S.; Bartelsman, J.F.W.M.; Dallinga-Thie, G.M.; Ackermans, M.T.; Serlie, M.J.; Oozeer, R.; Derrien, M.; Druesne, A.; Van Hylckama Vlieg, J.E.; Bloks, V.W.; Groen, A.K.; Heilig, H.G.; Zoetendal, E.G.; Stroes, E.S.; de Vos, W.M.; Hoekstra, J.B.; Nieuwdorp, M. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology, 2012, 143(4), 913-6.e7.
[http://dx.doi.org/10.1053/j.gastro.2012.06.031] [PMID: 22728514]
[120]
Brown, J.M.; Hazen, S.L. The gut microbial endocrine organ: Bacterially derived signals driving cardiometabolic diseases. Annu. Rev. Med., 2015, 66, 343-359.
[http://dx.doi.org/10.1146/annurev-med-060513-093205] [PMID: 25587655]
[121]
Fan, Y.; Pedersen, O. Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol., 2021, 19(1), 55-71.
[PMID: 32887946]
[122]
Currò, D. The role of gut microbiota in the modulation of drug action: A focus on some clinically significant issues. Expert Rev. Clin. Pharmacol., 2018, 11(2), 171-183.
[http://dx.doi.org/10.1080/17512433.2018.1414598] [PMID: 29210311]
[123]
Zhang, J.; Zhang, J.; Wang, R. Gut microbiota modulates drug pharmacokinetics. Drug Metab. Rev., 2018, 50(3), 357-368.
[http://dx.doi.org/10.1080/03602532.2018.1497647] [PMID: 30227749]
[124]
Toghi, M.; Bitarafan, S. Simvastatin therapy in multiple sclerosis patients with respect to gut microbiome-friend or foe? J. Neuroimmune Pharmacol., 2019, 14(4), 531-533.
[http://dx.doi.org/10.1007/s11481-019-09881-y] [PMID: 31628587]
[125]
Liu, Y.; Song, X.; Zhou, H.; Zhou, X.; Xia, Y.; Dong, X.; Zhong, W.; Tang, S.; Wang, L.; Wen, S.; Xiao, J.; Tang, L. Gut microbiome associates with lipid-lowering effect of rosuvastatin in vivo. Front. Microbiol., 2018, 9, 530.
[http://dx.doi.org/10.3389/fmicb.2018.00530] [PMID: 29623075]
[126]
Dias, A.M.; Cordeiro, G.; Estevinho, M.M.; Veiga, R.; Figueira, L.; Reina-Couto, M.; Magro, F. Gut bacterial microbiome composition and statin intake-A systematic review. Pharmacol. Res. Perspect., 2020, 8(3), e00601.
[127]
Moludi, J.; Saiedi, S.; Ebrahimi, B.; Alizadeh, M.; Khajebishak, Y.; Ghadimi, S.S. Probiotics supplementation on cardiac remodeling following myocardial infarction: A single-center double-blind clinical study. J. Cardiovasc. Transl. Res., 2021, 14(2), 299-307.
[http://dx.doi.org/10.1007/s12265-020-10052-1] [PMID: 32681453]

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