摘要
血管老化是动脉粥样硬化缺血性卒中的重要危险因素。血管老化的特征是氧化应激、内皮功能障碍、炎症、内膜和中膜增厚,以及动脉僵硬的逐渐发展,以及其他病理生理特征。关于氧化应激,活性氧和氮的浓度增加与血管老化中的动脉粥样硬化缺血性卒中有关。此外,氧化应激与炎症反应有关。炎症通过“炎症想象”理论与衰老有关,其特征是应对各种压力源的能力下降,同时促炎状态增加。血管老化与脑动脉变化相关,脑动脉变化被认为是动脉粥样硬化缺血性卒中风险的预测因素。本综述的目的是介绍氧化应激和炎症在血管老化中的作用,以及它们在动脉粥样硬化缺血性卒中中的作用。
关键词: 动脉粥样硬化缺血性中风、炎症、氧化应激、血管老化、ROS。
[1]
Ungvari, Z.; Tarantini, S.; Donato, A.J.; Galvan, V.; Csiszar, A. Mechanisms of vascular aging. Circ. Res., 2018, 123(7), 849-867.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.311378] [PMID: 30355080]
[http://dx.doi.org/10.1161/CIRCRESAHA.118.311378] [PMID: 30355080]
[2]
Ungvari, Z.; Tarantini, S.; Sorond, F.; Merkely, B.; Csiszar, A. Mechanisms of vascular aging, a gero-science perspective: JACC focus seminar. J. Am. Coll. Cardiol., 2020, 75(8), 931-941.
[http://dx.doi.org/10.1016/j.jacc.2019.11.061] [PMID: 32130929]
[http://dx.doi.org/10.1016/j.jacc.2019.11.061] [PMID: 32130929]
[3]
Seals, D.R.; Alexander, L.M. Vascular aging. J. Appl. Physiol., 2018, 125(6), 1841-1842.
[http://dx.doi.org/10.1152/japplphysiol.00448.2018] [PMID: 29878874]
[http://dx.doi.org/10.1152/japplphysiol.00448.2018] [PMID: 29878874]
[4]
Iadecola, C.; Buckwalter, M.S.; Anrather, J. Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J. Clin. Invest., 2020, 130(6), 2777-2788.
[http://dx.doi.org/10.1172/JCI135530] [PMID: 32391806]
[http://dx.doi.org/10.1172/JCI135530] [PMID: 32391806]
[5]
Kleindorfer, D.O.; Towfighi, A.; Chaturvedi, S.; Cockroft, K.M.; Gutierrez, J.; Lombardi-Hill, D.; Kamel, H.; Kernan, W.N.; Kittner, S.J.; Leira, E.C.; Lennon, O.; Meschia, J.F.; Nguyen, T.N.; Pollak, P.M.; Santangeli, P.; Sharrief, A.Z.; Smith, S.C.J., Jr; Turan, T.N.; Williams, L.S. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American heart association/American stroke association. Stroke, 2021, 52(7), e364-e467.
[http://dx.doi.org/10.1161/STR.0000000000000375] [PMID: 34024117]
[http://dx.doi.org/10.1161/STR.0000000000000375] [PMID: 34024117]
[6]
Leritz, E.C.; McGlinchey, R.E.; Kellison, I.; Rudolph, J.L.; Milberg, W.P. Cardiovascular disease risk factors and cognition in the elderly. Curr. Cardiovasc. Risk Rep., 2011, 5(5), 407-412.
[http://dx.doi.org/10.1007/s12170-011-0189-x] [PMID: 22199992]
[http://dx.doi.org/10.1007/s12170-011-0189-x] [PMID: 22199992]
[7]
Gustafsson, T.; Ulfhake, B. Sarcopenia: what is the origin of this aging-induced disorder? Front. Genet., 2021, 12(July), 688526.
[http://dx.doi.org/10.3389/fgene.2021.688526] [PMID: 34276788]
[http://dx.doi.org/10.3389/fgene.2021.688526] [PMID: 34276788]
[8]
Yousufuddin, M.; Bartley, A.C.; Alsawas, M.; Sheely, H.L.; Shultz, J.; Takahashi, P.Y.; Young, N.P.; Murad, M.H. Impact of multiple chronic conditions in patients hospitalized with stroke and transient is-chemic attack. Dis. Off. J. Natl. Stroke Assoc., 2017, 26(6), 1239-1248.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.01.015] [PMID: 28285088]
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.01.015] [PMID: 28285088]
[9]
Xu, X.; Wang, B.; Ren, C.; Hu, J.; Greenberg, D.A.; Chen, T.; Xie, L.; Jin, K. Recent progress in vas-cular aging: mechanisms and its role in age-related diseases. Aging Dis., 2017, 8(4), 486-505.
[http://dx.doi.org/10.14336/AD.2017.0507] [PMID: 28840062]
[http://dx.doi.org/10.14336/AD.2017.0507] [PMID: 28840062]
[10]
El Assar, M.; Angulo, J.; Rodríguez-Mañas, L. Oxidative stress and vascular inflammation in aging. Free Radic. Biol. Med., 2013, 65, 380-401.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.003] [PMID: 23851032]
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.003] [PMID: 23851032]
[11]
Harvey, A.; Montezano, A.C.; Touyz, R.M. Vascular biology of ageing-implications in hypertension. J. Mol. Cell. Cardiol., 2015, 83, 112-121.
[http://dx.doi.org/10.1016/j.yjmcc.2015.04.011] [PMID: 25896391]
[http://dx.doi.org/10.1016/j.yjmcc.2015.04.011] [PMID: 25896391]
[12]
Kattoor, A.J.; Pothineni, N.V.K.; Palagiri, D.; Mehta, J.L. Oxidative stress in atherosclerosis. Curr. Atheroscler. Rep., 2017, 19
[http://dx.doi.org/10.1007/s11883-017-0678-6]
[http://dx.doi.org/10.1007/s11883-017-0678-6]
[13]
Incalza, M.A.; 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]
[http://dx.doi.org/10.1016/j.vph.2017.05.005] [PMID: 28579545]
[14]
Donato, A.J.; Machin, D.R.; Lesniewski, L.A. Mechanisms of dysfunction in the aging vasculature and role in age-related disease. Circ. Res., 2018, 123(7), 825-848.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.312563] [PMID: 30355078]
[http://dx.doi.org/10.1161/CIRCRESAHA.118.312563] [PMID: 30355078]
[15]
Shahul, S.; Tung, A.; Minhaj, M.; Nizamuddin, J.; Wenger, J.; Mahmood, E.; Mueller, A.; Shaefi, S.; Scavone, B.; Kociol, R.D.; Talmor, D.; Rana, S. ROS/RNS of Cardiovas Tissues;, 2017, 176.
[http://dx.doi.org/10.1161/RES.0000000000000110.Measurement]
[http://dx.doi.org/10.1161/RES.0000000000000110.Measurement]
[16]
Puca, A.A.; Carrizzo, A.; Villa, F.; Ferrario, A.; Casaburo, M.; Maciąg, A.; Vecchione, C. Vascular ageing: the role of oxidative stress. Int. J. Biochem. Cell Biol., 2013, 45(3), 556-559.
[http://dx.doi.org/10.1016/j.biocel.2012.12.024] [PMID: 23305730]
[http://dx.doi.org/10.1016/j.biocel.2012.12.024] [PMID: 23305730]
[17]
Davalli, P.; Mitic, T.; Caporali, A.; Lauriola, A.; D’Arca, D. ROS, Cell senescence, and novel molecu-lar mechanisms in aging and age-related diseases. Oxid. Med. Cell. Longev., 2016, 2016, 3565127.
[http://dx.doi.org/10.1155/2016/3565127] [PMID: 27247702]
[http://dx.doi.org/10.1155/2016/3565127] [PMID: 27247702]
[18]
Allen, C.L.; Bayraktutan, U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int. J. Stroke, 2009, 4(6), 461-470.
[http://dx.doi.org/10.1111/j.1747-4949.2009.00387.x] [PMID: 19930058]
[http://dx.doi.org/10.1111/j.1747-4949.2009.00387.x] [PMID: 19930058]
[19]
Dikalov, S.I.; Nazarewicz, R.R. Angiotensin II-induced production of mitochondrial reactive oxygen species: potential mechanisms and relevance for cardiovascular disease. Antioxid. Redox Signal., 2013, 19(10), 1085-1094.
[http://dx.doi.org/10.1089/ars.2012.4604] [PMID: 22443458]
[http://dx.doi.org/10.1089/ars.2012.4604] [PMID: 22443458]
[20]
Cao, Q.; Wu, J.; Wang, X.; Song, C. Noncoding RNAs in vascular aging. Oxid. Med. Cell. Longev., 2020, 2020, 7914957.
[http://dx.doi.org/10.1155/2020/7914957] [PMID: 31998442]
[http://dx.doi.org/10.1155/2020/7914957] [PMID: 31998442]
[21]
Radi, R. Peroxynitrite, a stealthy biological oxidant. J. Biol. Chem., 2013, 288(37), 26464-26472.
[http://dx.doi.org/10.1074/jbc.R113.472936] [PMID: 23861390]
[http://dx.doi.org/10.1074/jbc.R113.472936] [PMID: 23861390]
[22]
Adams, L.; Franco, M.C.; Estevez, A.G. Reactive nitrogen species in cellular signaling. Exp. Biol. Med. (Maywood), 2015, 240(6), 711-717.
[http://dx.doi.org/10.1177/1535370215581314] [PMID: 25888647]
[http://dx.doi.org/10.1177/1535370215581314] [PMID: 25888647]
[23]
Pacher, P.; Beckman, J.S.; Liaudet, L. Nitric oxide and peroxynitrite in health and disease. Physiol. Rev., 2007, 87(1), 315-424.
[http://dx.doi.org/10.1152/physrev.00029.2006] [PMID: 17237348]
[http://dx.doi.org/10.1152/physrev.00029.2006] [PMID: 17237348]
[24]
Donato, A.J.; Eskurza, I.; Silver, A.E.; Levy, A.S.; Pierce, G.L.; Gates, P.E.; Seals, D.R. Direct evi-dence 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]
[http://dx.doi.org/10.1161/01.RES.0000269183.13937.e8] [PMID: 17478731]
[25]
Akhmedov, A.; Sawamura, T.; Chen, C-H.; Kraler, S.; Vdovenko, D.; Lüscher, T.F. Lectin-like oxi-dized low-density lipoprotein receptor-1 (LOX-1): a crucial driver of atherosclerotic cardiovascular dis-ease. Eur. Heart J., 2020, 1, 1-11.
[http://dx.doi.org/10.1093/eurheartj/ehaa770] [PMID: 33159784]
[http://dx.doi.org/10.1093/eurheartj/ehaa770] [PMID: 33159784]
[26]
Massaro, M.; Scoditti, E.; Carluccio, M.A.; De Caterina, R. Oxidative stress and vascular stiffness in hypertension: A renewed interest for antioxidant therapies? Vascul. Pharmacol., 2019, 116, 45-50.
[http://dx.doi.org/10.1016/j.vph.2019.03.004] [PMID: 30946986]
[http://dx.doi.org/10.1016/j.vph.2019.03.004] [PMID: 30946986]
[27]
Lehner, C.; Gehwolf, R.; Tempfer, H.; Krizbai, I.; Hennig, B.; Bauer, H.C.; Bauer, H. Oxidative stress and blood-brain barrier dysfunction under particular consideration of matrix metalloproteinases. Antioxid. Redox Signal., 2011, 15(5), 1305-1323.
[http://dx.doi.org/10.1089/ars.2011.3923] [PMID: 21294658]
[http://dx.doi.org/10.1089/ars.2011.3923] [PMID: 21294658]
[28]
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]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.07802] [PMID: 28784646]
[29]
Durrant, J.R.; Seals, D.R.; Connell, M.L.; Russell, M.J.; Lawson, B.R.; Folian, B.J.; Donato, A.J.; Le-sniewski, L.A. Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase. J. Physiol., 2009, 587(Pt 13), 3271-3285.
[http://dx.doi.org/10.1113/jphysiol.2009.169771] [PMID: 19417091]
[http://dx.doi.org/10.1113/jphysiol.2009.169771] [PMID: 19417091]
[30]
Yokoyama, M.; Hirata, K. Endothelial nitric oxide synthase uncoupling: Is it a physiological mecha-nism of endothelium-dependent relaxation in cerebral artery? Cardiovasc. Res., 2007, 73(1), 8-9.
[http://dx.doi.org/10.1016/j.cardiores.2006.11.009] [PMID: 17156766]
[http://dx.doi.org/10.1016/j.cardiores.2006.11.009] [PMID: 17156766]
[31]
Seals, D.R.; Jablonski, K.L.; Donato, A.J. Aging and vascular endothelial function in humans. Clin. Sci. (Lond.), 2011, 120(9), 357-375.
[http://dx.doi.org/10.1042/CS20100476] [PMID: 21244363]
[http://dx.doi.org/10.1042/CS20100476] [PMID: 21244363]
[32]
Laina, A.; Stellos, K.; Stamatelopoulos, K. Vascular ageing: Underlying mechanisms and clinical im-plications. Exp. Gerontol., 2018, 109, 16-30.
[http://dx.doi.org/10.1016/j.exger.2017.06.007] [PMID: 28624356]
[http://dx.doi.org/10.1016/j.exger.2017.06.007] [PMID: 28624356]
[33]
Chen, S.; Li, N.; Deb-Chatterji, M.; Dong, Q.; Kielstein, J.T.; Weissenborn, K.; Worthmann, H. Asymmetric dimethyarginine as marker and mediator in ischemic stroke. Int. J. Mol. Sci., 2012, 13(12), 15983-16004.
[http://dx.doi.org/10.3390/ijms131215983] [PMID: 23443106]
[http://dx.doi.org/10.3390/ijms131215983] [PMID: 23443106]
[34]
Nishiyama, Y.; Ueda, M.; Katsura, K.; Otsuka, T.; Abe, A.; Nagayama, H.; Katayama, Y. Asymmet-ric dimethylarginine (ADMA) as a possible risk marker for ischemic stroke. J. Neurol. Sci., 2010, 290(1-2), 12-15.
[http://dx.doi.org/10.1016/j.jns.2009.12.020] [PMID: 20060545]
[http://dx.doi.org/10.1016/j.jns.2009.12.020] [PMID: 20060545]
[35]
Costantino, S.; Paneni, F.; Cosentino, F. Ageing, metabolism and cardiovascular disease. J. Physiol., 2016, 594(8), 2061-2073.
[http://dx.doi.org/10.1113/JP270538] [PMID: 26391109]
[http://dx.doi.org/10.1113/JP270538] [PMID: 26391109]
[36]
Csiszar, A.; Gautam, T.; Sosnowska, D.; Tarantini, S.; Banki, E.; Tucsek, Z.; Toth, P.; Losonczy, G.; Koller, A.; Reglodi, D.; Giles, C.B.; Wren, J.D.; Sonntag, W.E.; Ungvari, Z. Caloric restriction confers persistent anti-oxidative, pro-angiogenic, and anti-inflammatory effects and promotes anti-aging miRNA expression profile in cerebromicrovascular endothelial cells of aged rats. Am. J. Physiol. Heart Circ. Physiol., 2014, 307(3), H292-H306.
[http://dx.doi.org/10.1152/ajpheart.00307.2014] [PMID: 24906921]
[http://dx.doi.org/10.1152/ajpheart.00307.2014] [PMID: 24906921]
[37]
Moldogazieva, N.T.; Mokhosoev, I.M.; Mel’nikova, T.I.; Porozov, Y.B.; Terentiev, A.A. Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxid. Med. Cell. Longev., 2019, 2019, 3085756.
[http://dx.doi.org/10.1155/2019/3085756] [PMID: 31485289]
[http://dx.doi.org/10.1155/2019/3085756] [PMID: 31485289]
[38]
Ungvari, Z.; Bailey-Downs, L.; Sosnowska, D.; Gautam, T.; Koncz, P.; Losonczy, G.; Ballabh, P.; de Cabo, R.; Sonntag, W.E.; Csiszar, A. Vascular oxidative stress in aging: A homeostatic failure due to dysregulation of NRF2-mediated antioxidant response. Am. J. Physiol. Heart Circ. Physiol., 2011, 301(2), H363-H372.
[http://dx.doi.org/10.1152/ajpheart.01134.2010] [PMID: 21602469]
[http://dx.doi.org/10.1152/ajpheart.01134.2010] [PMID: 21602469]
[39]
Chiriacò, M.; Georgiopoulos, G.; Duranti, E.; Antonioli, L.; Puxeddu, I.; Nannipieri, M.; Rosada, J.; Blandizzi, C.; Taddei, S.; Virdis, A.; Masi, S. Inflammation and vascular ageing: from telomeres to novel emerging mechanisms. High Blood Press. Cardiovasc. Prev., 2019, 26(4), 321-329.
[http://dx.doi.org/10.1007/s40292-019-00331-7] [PMID: 31325087]
[http://dx.doi.org/10.1007/s40292-019-00331-7] [PMID: 31325087]
[40]
Franceschi, C.; Bonafè, M.; Valensin, S.; Olivieri, F.; De Luca, M.; Ottaviani, E.; De Benedictis, G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci., 2000, 908, 244-254.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06651.x] [PMID: 10911963]
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06651.x] [PMID: 10911963]
[41]
Ventura, M.T.; Casciaro, M.; Gangemi, S.; Buquicchio, R. Immunosenescence in aging: between im-mune cells depletion and cytokines up-regulation. Clin. Mol. Allergy, 2017, 15, 21.
[http://dx.doi.org/10.1186/s12948-017-0077-0] [PMID: 29259496]
[http://dx.doi.org/10.1186/s12948-017-0077-0] [PMID: 29259496]
[42]
de Almeida, A.J.P.O.; de Almeida Rezende, M.S.; Dantas, S.H.; de Lima Silva, S.; de Oliveira, J.C.P.L.; de Lourdes Assunção Araújo de Azevedo, F.; Alves, R.M.F.R.; de Menezes, G.M.S.; Dos San-tos, P.F.; Gonçalves, T.A.F.; Schini-Kerth, V.B.; de Medeiros, I.A. Unveiling the role of inflammation and oxidative stress on age-related cardiovascular diseases. Oxid. Med. Cell. Longev., 2020, 2020, 1954398.
[http://dx.doi.org/10.1155/2020/1954398] [PMID: 32454933]
[http://dx.doi.org/10.1155/2020/1954398] [PMID: 32454933]
[43]
Ershler, W.B. Interleukin-6: A cytokine for gerontologists. J. Am. Geriatr. Soc., 1993, 41(2), 176-181.
[http://dx.doi.org/10.1111/j.1532-5415.1993.tb02054.x] [PMID: 8426042]
[http://dx.doi.org/10.1111/j.1532-5415.1993.tb02054.x] [PMID: 8426042]
[44]
Bruunsgaard, H.; Andersen-Ranberg, K.; Jeune, B.; Pedersen, A.N.; Skinhøj, P.; Pedersen, B.K. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J. Gerontol. A Biol. Sci. Med. Sci., 1999, 54(7), M357-M364.
[http://dx.doi.org/10.1093/gerona/54.7.M357] [PMID: 10462168]
[http://dx.doi.org/10.1093/gerona/54.7.M357] [PMID: 10462168]
[45]
Cohen, H.J.; Pieper, C.F.; Harris, T.; Rao, K.M.; Currie, M.S. The association of plasma IL-6 levels with functional disability in community-dwelling elderly. J. Gerontol. A Biol. Sci. Med. Sci., 1997, 52(4), M201-M208.
[http://dx.doi.org/10.1093/gerona/52A.4.M201] [PMID: 9224431]
[http://dx.doi.org/10.1093/gerona/52A.4.M201] [PMID: 9224431]
[46]
Fagiolo, U.; Cossarizza, A.; Scala, E.; Fanales-Belasio, E.; Ortolani, C.; Cozzi, E.; Monti, D.; Frances-chi, C.; Paganelli, R. Increased cytokine production in mononuclear cells of healthy elderly people. Eur. J. Immunol., 1993, 23(9), 2375-2378.
[http://dx.doi.org/10.1002/eji.1830230950] [PMID: 8370415]
[http://dx.doi.org/10.1002/eji.1830230950] [PMID: 8370415]
[47]
Ferrucci, L.; Corsi, A.; Lauretani, F.; Bandinelli, S.; Bartali, B.; Taub, D.D.; Guralnik, J.M.; Longo, D.L. The origins of age-related proinflammatory state. Blood, 2005, 105(6), 2294-2299.
[http://dx.doi.org/10.1182/blood-2004-07-2599] [PMID: 15572589]
[http://dx.doi.org/10.1182/blood-2004-07-2599] [PMID: 15572589]
[48]
Michaud, M.; Balardy, L.; Moulis, G.; Gaudin, C.; Peyrot, C.; Vellas, B.; Cesari, M.; Nourhashemi, F. Proinflammatory cytokines, aging, and age-related diseases. J. Am. Med. Dir. Assoc., 2013, 14(12), 877-882.
[http://dx.doi.org/10.1016/j.jamda.2013.05.009] [PMID: 23792036]
[http://dx.doi.org/10.1016/j.jamda.2013.05.009] [PMID: 23792036]
[49]
Menghini, R.; Stöhr, R.; Federici, M. MicroRNAs in vascular aging and atherosclerosis. Ageing Res. Rev., 2014, 17, 68-78.
[http://dx.doi.org/10.1016/j.arr.2014.03.005] [PMID: 24681293]
[http://dx.doi.org/10.1016/j.arr.2014.03.005] [PMID: 24681293]
[50]
Scuteri, A.; Orru, M.; Morrell, C.; Piras, M.G.; Taub, D.; Schlessinger, D.; Uda, M.; Lakatta, E.G. In-dependent and additive effects of cytokine patterns and the metabolic syndrome on arterial aging in the SardiNIA Study. Atherosclerosis, 2011, 215(2), 459-464.
[http://dx.doi.org/10.1016/j.atherosclerosis.2010.12.023] [PMID: 21241986]
[http://dx.doi.org/10.1016/j.atherosclerosis.2010.12.023] [PMID: 21241986]
[51]
Freund, A.; Orjalo, A.V.; Desprez, P-Y.; Campisi, J. Inflammatory networks during cellular senes-cence: causes and consequences. Trends Mol. Med., 2010, 16(5), 238-246.
[http://dx.doi.org/10.1016/j.molmed.2010.03.003] [PMID: 20444648]
[http://dx.doi.org/10.1016/j.molmed.2010.03.003] [PMID: 20444648]
[52]
Fulop, T.; Larbi, A.; Dupuis, G.; Le Page, A.; Frost, E.H.; Cohen, A.A.; Witkowski, J.M.; Franceschi, C. Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes? Front. Immunol., 2018, 8, 1960.
[http://dx.doi.org/10.3389/fimmu.2017.01960] [PMID: 29375577]
[http://dx.doi.org/10.3389/fimmu.2017.01960] [PMID: 29375577]
[53]
Olivieri, F.; Prattichizzo, F.; Grillari, J.; Balistreri, C.R. Cellular Senescence and Inflammaging in Age-Related Diseases. Mediators Inflamm., 2018, 2018, 9076485.
[http://dx.doi.org/10.1155/2018/9076485] [PMID: 29849499]
[http://dx.doi.org/10.1155/2018/9076485] [PMID: 29849499]
[54]
Jia, G.; Aroor, A.R.; Jia, C.; Sowers, J.R. Endothelial cell senescence in aging-related vascular dys-function. Biochim. Biophys. Acta Mol. Basis Dis., 2019, 1865(7), 1802-1809.
[http://dx.doi.org/10.1016/j.bbadis.2018.08.008] [PMID: 31109450]
[http://dx.doi.org/10.1016/j.bbadis.2018.08.008] [PMID: 31109450]
[55]
Jia, G.; Aroor, A.R.; DeMarco, V.G.; Martinez-Lemus, L.A.; Meininger, G.A.; Sowers, J.R. Vascular stiffness in insulin resistance and obesity. Front. Physiol., 2015, 6, 231.
[http://dx.doi.org/10.3389/fphys.2015.00231] [PMID: 26321962]
[http://dx.doi.org/10.3389/fphys.2015.00231] [PMID: 26321962]
[56]
Uryga, A.K.; Bennett, M.R. Ageing induced vascular smooth muscle cell senescence in atherosclero-sis. J. Physiol., 2016, 594(8), 2115-2124.
[http://dx.doi.org/10.1113/JP270923] [PMID: 26174609]
[http://dx.doi.org/10.1113/JP270923] [PMID: 26174609]
[57]
López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. The hallmarks of aging. Cell, 2013, 153(6), 1194-1217.
[http://dx.doi.org/10.1016/j.cell.2013.05.039] [PMID: 23746838]
[http://dx.doi.org/10.1016/j.cell.2013.05.039] [PMID: 23746838]
[58]
Profaci, C.P.; Munji, R.N.; Pulido, R.S.; Daneman, R. The blood-brain barrier in health and disease: Important unanswered questions. J. Exp. Med., 2020, 217(4), 1-16.
[http://dx.doi.org/10.1084/jem.20190062] [PMID: 32211826]
[http://dx.doi.org/10.1084/jem.20190062] [PMID: 32211826]
[59]
Ungvari, Z.; Podlutsky, A.; Sosnowska, D.; Tucsek, Z.; Toth, P.; Deak, F.; Gautam, T.; Csiszar, A.; Sonntag, W. E. Ionizing radiation promotes the acquisition of a senescence-associated secretory phenotype and impairs angiogenic capacity in cerebromicrovascular endothelial cells: role of increased DNA damage and decreased DNA repair capacity in microvascular radiosens. Journals Gerontol. - Ser. A Biol. Sci. Med. Sci, 2013, 68(12 A), 1443-1457.
[http://dx.doi.org/10.1093/gerona/glt057]
[http://dx.doi.org/10.1093/gerona/glt057]
[60]
Morgan, R.G.; Ives, S.J.; Lesniewski, L.A.; Cawthon, R.M.; Andtbacka, R.H.I.; Noyes, R.D.; Rich-ardson, R.S.; Donato, A.J. Age-related telomere uncapping is associated with cellular senescence and in-flammation independent of telomere shortening in human arteries. Am. J. Physiol. Heart Circ. Physiol., 2013, 305(2), H251-H258.
[http://dx.doi.org/10.1152/ajpheart.00197.2013] [PMID: 23666675]
[http://dx.doi.org/10.1152/ajpheart.00197.2013] [PMID: 23666675]
[61]
Csiszar, A.; Wang, M.; Lakatta, E.G.; Ungvari, Z. Inflammation and endothelial dysfunction during aging: role of NF-kappaB. J. Appl. Physiol., 2008, 105(4), 1333-1341.
[http://dx.doi.org/10.1152/japplphysiol.90470.2008] [PMID: 18599677]
[http://dx.doi.org/10.1152/japplphysiol.90470.2008] [PMID: 18599677]
[62]
Csiszar, A.; Ungvari, Z.; Koller, A.; Edwards, J.G.; Kaley, G. Proinflammatory phenotype of coro-nary arteries promotes endothelial apoptosis in aging. Physiol. Genomics, 2004, 17(1), 21-30.
[http://dx.doi.org/10.1152/physiolgenomics.00136.2003] [PMID: 15020720]
[http://dx.doi.org/10.1152/physiolgenomics.00136.2003] [PMID: 15020720]
[63]
Cernadas, M.R.; Sánchez de Miguel, L.; García-Durán, M.; González-Fernández, F.; Millás, I.; Montón, M.; Rodrigo, J.; Rico, L.; Fernández, P.; de Frutos, T.; Rodríguez-Feo, J.A.; Guerra, J.; Caramelo, C.; Casado, S. López-Farré, Expression of constitutive and inducible nitric oxide synthases in the vascular wall of young and aging rats. Circ. Res., 1998, 83(3), 279-286.
[http://dx.doi.org/10.1161/01.RES.83.3.279] [PMID: 9710120]
[http://dx.doi.org/10.1161/01.RES.83.3.279] [PMID: 9710120]
[64]
Ungvari, Z.; Orosz, Z.; Labinskyy, N.; Rivera, A.; Xiangmin, Z.; Smith, K.; Csiszar, A. Increased mi-tochondrial H2O2 production promotes endothelial NF-kappaB activation in aged rat arteries. Am. J. Physiol. Heart Circ. Physiol., 2007, 293(1), H37-H47.
[http://dx.doi.org/10.1152/ajpheart.01346.2006] [PMID: 17416599]
[http://dx.doi.org/10.1152/ajpheart.01346.2006] [PMID: 17416599]
[65]
Ungvari, Z.; Labinskyy, N.; Gupte, S.; Chander, P.N.; Edwards, J.G.; Csiszar, A. Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats. Am. J. Physiol. Heart Circ. Physiol., 2008, 294(5), H2121-H2128.
[http://dx.doi.org/10.1152/ajpheart.00012.2008] [PMID: 18326800]
[http://dx.doi.org/10.1152/ajpheart.00012.2008] [PMID: 18326800]
[66]
Assar, M.E.; Angulo, J.; Rodríguez-Mañas, L. Diabetes and ageing-induced vascular inflammation. J. Physiol., 2016, 594(8), 2125-2146.
[http://dx.doi.org/10.1113/JP270841] [PMID: 26435167]
[http://dx.doi.org/10.1113/JP270841] [PMID: 26435167]
[67]
Deepa, S.S.; Unnikrishnan, A.; Matyi, S.; Hadad, N.; Richardson, A. Necroptosis increases with age and is reduced by dietary restriction. Aging Cell, 2018, 17(4), e12770.
[http://dx.doi.org/10.1111/acel.12770] [PMID: 29696779]
[http://dx.doi.org/10.1111/acel.12770] [PMID: 29696779]
[68]
Abbafati, C.; Abbas, K.M.; Abbasi-Kangevari, M.; Abd-Allah, F.; Abdelalim, A.; Abdollahi, M.; Abdollahpour, I.; Abegaz, K.H.; Abolhassani, H.; Aboyans, V.; Abreu, L.G.; Abrigo, M.R.M.; Abualha-san, A.; Abu-Raddad, L.J.; Abushouk, A.I.; Adabi, M.; Adekanmbi, V.; Adeoye, A.M.; Adetokunboh, O.O.; Adham, D.; Advani, S.M.; Afshin, A.; Agarwal, G.; Aghamir, S.M.K.; Agrawal, A.; Ahmad, T.; Ahmadi, K.; Ahmadi, M.; Ahmadieh, H.; Ahmed, M.B.; Akalu, T.Y.; Akinyemi, R.O.; Akinyemiju, T.; Akombi, B.; Akunna, C.J.; Alahdab, F.; Al-Aly, Z.; Alam, K.; Alam, S.; Alam, T.; Alanezi, F.M.; Alanzi, T.M.; Alemu, B.W.; Alhabib, K.F.; Ali, M.; Ali, S.; Alicandro, G.; Alinia, C.; Alipour, V.; Alizade, H.; Aljunid, S.M.; Alla, F.; Allebeck, P.; Almasi-Hashiani, A.; Al-Mekhlafi, H.M.; Alonso, J.; Altirkawi, K.A.; Amini-Rarani, M.; Amiri, F.; Amugsi, D.A.; Ancuceanu, R.; Anderlini, D.; Anderson, J.A.; Andrei, C.L.; Andrei, T.; Angus, C.; Anjomshoa, M.; Ansari, F.; Ansari-Moghaddam, A.; Antonazzo, I.C.; Antonio, C.A.T.; Antony, C.M.; Antriyandarti, E.; Anvari, D.; Anwer, R.; Appiah, S.C.Y.; Arabloo, J.; Arab-Zozani, M.; Aravkin, A.Y.; Ariani, F.; Armoon, B.; Ärnlöv, J.; Arzani, A.; Asadi-Aliabadi, M.; Asadi-Pooya, A.A.; Ashbaugh, C.; Assmus, M.; Atafar, Z.; Atnafu, D.D.; Atout, M.M.W.; Ausloos, F.; Ausloos, M.; Ayala Quintanilla, B.P.; Ayano, G.; Ayanore, M.A.; Azari, S.; Azarian, G.; Azene, Z.N.; Badawi, A.; Badiye, A.D.; Bahrami, M.A.; Bakhshaei, M.H.; Bakhtiari, A.; Bakkannavar, S.M.; Baldasseroni, A.; Ball, K.; Ballew, S.H.; Balzi, D.; Banach, M.; Banerjee, S.K.; Bante, A.B.; Baraki, A.G.; Barker-Collo, S.L.; Bärnighausen, T.W.; Barrero, L.H.; Barthelemy, C.M.; Barua, L.; Basu, S.; Baune, B.T.; Bayati, M.; Beck-er, J.S.; Bedi, N.; Beghi, E.; Béjot, Y.; Bell, M.L.; Bennitt, F.B.; Bensenor, I.M.; Berhe, K.; Berman, A.E.; Bhagavathula, A.S.; Bhageerathy, R.; Bhala, N.; Bhandari, D.; Bhattacharyya, K.; Bhutta, Z.A.; Bijani, A.; Bikbov, B.; Bin Sayeed, M.S.; Biondi, A.; Birihane, B.M.; Bisignano, C.; Biswas, R.K.; Bitew, H.; Bohlouli, S.; Bohluli, M.; Boon-Dooley, A.S.; Borges, G.; Borzì, A.M.; Borzouei, S.; Bosetti, C.; Boufous, S.; Braithwaite, D.; Brauer, M.; Breitborde, N.J.K.; Breitner, S.; Brenner, H.; Briant, P.S.; Briko, A.N.; Briko, N.I.; Britton, G.B.; Bryazka, D.; Bumgarner, B.R.; Burkart, K.; Burnett, R.T.; Burugina Nagaraja, S.; Butt, Z.A.; Caetano Dos Santos, F.L.; Cahill, L.E.; Cámera, L.A.; Campos-Nonato, I.R.; Cárdenas, R.; Carreras, G.; Carrero, J.J.; Carvalho, F.; Castaldelli-Maia, J.M.; Castañeda-Orjuela, C.A.; Castelpietra, G.; Castro, F.; Causey, K.; Cederroth, C.R.; Cercy, K.M.; Cerin, E.; Chandan, J.S.; Chang, K.L.; Charlson, F.J.; Chattu, V.K.; Chaturvedi, S.; Cherbuin, N.; Chimed-Ochir, O.; Cho, D.Y.; Choi, J.Y.J.; Christensen, H.; Chu, D.T.; Chung, M.T.; Chung, S.C.; Cicuttini, F.M.; Ciobanu, L.G.; Cirillo, M.; Classen, T.K.D.; Cohen, A.J.; Compton, K.; Cooper, O.R.; Costa, V.M.; Cousin, E.; Cowden, R.G.; Cross, D.H.; Cruz, J.A.; Dahlawi, S.M.A.; Damasceno, A.A.M.; Damiani, G.; Dandona, L.; Dandona, R.; Dangel, W.J.; Dan-ielsson, A.K.; Dargan, P.I.; Darwesh, A.M.; Daryani, A.; Das, J.K.; Das Gupta, R. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the global bur-den of disease study 2019. Lancet, 2020, 396(10258), 1204-1222.
[http://dx.doi.org/10.1016/S0140-6736(20)30925-9] [PMID: 33069326]
[http://dx.doi.org/10.1016/S0140-6736(20)30925-9] [PMID: 33069326]
[69]
Abbafati, C.; Abbas, K.M.; Abbasi-Kangevari, M.; Abd-Allah, F.; Abdelalim, A.; Abdollahi, M.; Abdollahpour, I.; Abegaz, K.H.; Abolhassani, H.; Aboyans, V.; Abreu, L.G.; Abrigo, M.R.M.; Abualha-san, A.; Abu-Raddad, L.J.; Abushouk, A.I.; Adabi, M.; Adekanmbi, V.; Adeoye, A.M.; Adetokunboh, O.O.; Adham, D.; Advani, S.M.; Afshin, A.; Agarwal, G.; Aghamir, S.M.K.; Agrawal, A.; Ahmad, T.; Ahmadi, K.; Ahmadi, M.; Ahmadieh, H.; Ahmed, M.B.; Akalu, T.Y.; Akinyemi, R.O.; Akinyemiju, T.; Akombi, B.; Akunna, C.J.; Alahdab, F.; Al-Aly, Z.; Alam, K.; Alam, S.; Alam, T.; Alanezi, F.M.; Alanzi, T.M.; Alemu, B.W.; Alhabib, K.F.; Ali, M.; Ali, S.; Alicandro, G.; Alinia, C.; Alipour, V.; Alizade, H.; Aljunid, S.M.; Alla, F.; Allebeck, P.; Almasi-Hashiani, A.; Al-Mekhlafi, H.M.; Alonso, J.; Altirkawi, K.A.; Amini-Rarani, M.; Amiri, F.; Amugsi, D.A.; Ancuceanu, R.; Anderlini, D.; Anderson, J.A.; Andrei, C.L.; Andrei, T.; Angus, C.; Anjomshoa, M.; Ansari, F.; Ansari-Moghaddam, A.; Antonazzo, I.C.; Antonio, C.A.T.; Antony, C.M.; Antriyandarti, E.; Anvari, D.; Anwer, R.; Appiah, S.C.Y.; Arabloo, J.; Arab-Zozani, M.; Aravkin, A.Y.; Ariani, F.; Armoon, B.; Ärnlöv, J.; Arzani, A.; Asadi-Aliabadi, M.; Asadi-Pooya, A.A.; Ashbaugh, C.; Assmus, M.; Atafar, Z.; Atnafu, D.D.; Atout, M.M.W.; Ausloos, F.; Ausloos, M.; Ayala Quintanilla, B.P.; Ayano, G.; Ayanore, M.A.; Azari, S.; Azarian, G.; Azene, Z.N.; Badawi, A.; Badiye, A.D.; Bahrami, M.A.; Bakhshaei, M.H.; Bakhtiari, A.; Bakkannavar, S.M.; Baldasseroni, A.; Ball, K.; Ballew, S.H.; Balzi, D.; Banach, M.; Banerjee, S.K.; Bante, A.B.; Baraki, A.G.; Barker-Collo, S.L.; Bärnighausen, T.W.; Barrero, L.H.; Barthelemy, C.M.; Barua, L.; Basu, S.; Baune, B.T.; Bayati, M.; Beck-er, J.S.; Bedi, N.; Beghi, E.; Béjot, Y.; Bell, M.L.; Bennitt, F.B.; Bensenor, I.M.; Berhe, K.; Berman, A.E.; Bhagavathula, A.S.; Bhageerathy, R.; Bhala, N.; Bhandari, D.; Bhattacharyya, K.; Bhutta, Z.A.; Bijani, A.; Bikbov, B.; Bin Sayeed, M.S.; Biondi, A.; Birihane, B.M.; Bisignano, C.; Biswas, R.K.; Bitew, H.; Bohlouli, S.; Bohluli, M.; Boon-Dooley, A.S.; Borges, G.; Borzì, A.M.; Borzouei, S.; Bosetti, C.; Boufous, S.; Braithwaite, D.; Brauer, M.; Breitborde, N.J.K.; Breitner, S.; Brenner, H.; Briant, P.S.; Briko, A.N.; Briko, N.I.; Britton, G.B.; Bryazka, D.; Bumgarner, B.R.; Burkart, K.; Burnett, R.T.; Burugina Nagaraja, S.; Butt, Z.A.; Caetano Dos Santos, F.L.; Cahill, L.E.; Cámera, L.A.; Campos-Nonato, I.R.; Cárdenas, R.; Carreras, G.; Carrero, J.J.; Carvalho, F.; Castaldelli-Maia, J.M.; Castañeda-Orjuela, C.A.; Castelpietra, G.; Castro, F.; Causey, K.; Cederroth, C.R.; Cercy, K.M.; Cerin, E.; Chandan, J.S.; Chang, K.L.; Charlson, F.J.; Chattu, V.K.; Chaturvedi, S.; Cherbuin, N.; Chimed-Ochir, O.; Cho, D.Y.; Choi, J.Y.J.; Christensen, H.; Chu, D.T.; Chung, M.T.; Chung, S.C.; Cicuttini, F.M.; Ciobanu, L.G.; Cirillo, M.; Classen, T.K.D.; Cohen, A.J.; Compton, K.; Cooper, O.R.; Costa, V.M.; Cousin, E.; Cowden, R.G.; Cross, D.H.; Cruz, J.A.; Dahlawi, S.M.A.; Damasceno, A.A.M.; Damiani, G.; Dandona, L.; Dandona, R.; Dangel, W.J.; Dan-ielsson, A.K.; Dargan, P.I.; Darwesh, A.M.; Daryani, A.; Das, J.K.; Das Gupta, R. Global burden of 87 risk factors in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 2020, 396(10258), 1223-1249.
[http://dx.doi.org/10.1016/S0140-6736(20)30752-2] [PMID: 33069327]
[http://dx.doi.org/10.1016/S0140-6736(20)30752-2] [PMID: 33069327]
[70]
Lakatta, E.G.; Levy, D. Arterial and cardiac aging: major shareholders in cardiovascular disease en-terprises: Part I: Aging arteries: A “set up” for vascular disease. Circulation, 2003, 107(1), 139-146.
[http://dx.doi.org/10.1161/01.CIR.0000048892.83521.58] [PMID: 12515756]
[http://dx.doi.org/10.1161/01.CIR.0000048892.83521.58] [PMID: 12515756]
[71]
O’Donnell, M.J.; Xavier, D.; Liu, L.; Zhang, H.; Chin, S.L.; Rao-Melacini, P.; Rangarajan, S.; Islam, S.; Pais, P.; McQueen, M.J.; Mondo, C.; Damasceno, A.; Lopez-Jaramillo, P.; Hankey, G.J. Dans, A.L.; Yusoff, K.; Truelsen, T.; Diener, H.C.; Sacco, R.L.; Ryglewicz, D.; Czlonkowska, A.; Weimar, C.; Wang, X.; Yusuf, S. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the IN-TERSTROKE study): A case-control study. Lancet, 2010, 376(9735), 112-123.
[http://dx.doi.org/10.1016/S0140-6736(10)60834-3] [PMID: 20561675]
[http://dx.doi.org/10.1016/S0140-6736(10)60834-3] [PMID: 20561675]
[72]
Yousufuddin, M.; Young, N. Aging and ischemic stroke. Aging (Albany NY), 2019, 11(9), 2542-2544.
[http://dx.doi.org/10.18632/aging.101931] [PMID: 31043575]
[http://dx.doi.org/10.18632/aging.101931] [PMID: 31043575]
[73]
Béjot, Y.; Bailly, H.; Graber, M.; Garnier, L.; Laville, A.; Dubourget, L.; Mielle, N.; Chevalier, C.; Durier, J.; Giroud, M. Impact of the ageing population on the burden of stroke: the dijon stroke registry. Neuroepidemiology, 2019, 52(1-2), 78-85.
[http://dx.doi.org/10.1159/000492820] [PMID: 30602168]
[http://dx.doi.org/10.1159/000492820] [PMID: 30602168]
[74]
Camici, L.L. The role of vascular aging in atherosclerotic plaque development and vulnerability. Curr. Pharm. Des., 2019, 3098-3111.
[http://dx.doi.org/10.2174/1381612825666190830175424]
[http://dx.doi.org/10.2174/1381612825666190830175424]
[75]
Shah, A.V.; Bennett, M.R. DNA damage-dependent mechanisms of ageing and disease in the macro- and microvasculature. Eur. J. Pharmacol., 2017, 816(816), 116-128.
[http://dx.doi.org/10.1016/j.ejphar.2017.03.050] [PMID: 28347738]
[http://dx.doi.org/10.1016/j.ejphar.2017.03.050] [PMID: 28347738]
[76]
Chi, C.; Li, D.J.; Jiang, Y.J.; Tong, J.; Fu, H.; Wu, Y.H.; Shen, F.M. Vascular smooth muscle cell se-nescence and age-related diseases: State of the art. Biochim. Biophys. Acta Mol. Basis Dis., 2019, 1865(7), 1810-1821.
[http://dx.doi.org/10.1016/j.bbadis.2018.08.015] [PMID: 31109451]
[http://dx.doi.org/10.1016/j.bbadis.2018.08.015] [PMID: 31109451]
[77]
Rovillain, E.; Mansfield, L.; Lord, C.J.; Ashworth, A.; Jat, P.S. An RNA interference screen for iden-tifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence. BMC Genomics, 2011, 12, 355.
[http://dx.doi.org/10.1186/1471-2164-12-355] [PMID: 21740549]
[http://dx.doi.org/10.1186/1471-2164-12-355] [PMID: 21740549]
[78]
Kobashigawa, S.M.; Sakaguchi, Y.; Masunaga, S.; Mori, E. Stress-induced cellular senescence con-tributes to chronic inflammation and cancer progression. Therm. Med., 2019, 35(4), 41-58.
[http://dx.doi.org/10.3191/thermalmed.35.41]
[http://dx.doi.org/10.3191/thermalmed.35.41]
[79]
Liu, X.; Wan, M. A Tale of the good and bad: cell senescence in bone homeostasis and disease. International Review of Cell and Molecular Biology, Galluzzi, L., Ed.; Academic Press,. 2019, 346, 97-128.
[http://dx.doi.org/10.1016/bs.ircmb.2019.03.005]
[http://dx.doi.org/10.1016/bs.ircmb.2019.03.005]
[80]
Kumari, R.; Jat, P. Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype. Front. Cell Dev. Biol., 2021, 9(March), 645593.
[http://dx.doi.org/10.3389/fcell.2021.645593] [PMID: 33855023]
[http://dx.doi.org/10.3389/fcell.2021.645593] [PMID: 33855023]
[81]
McConnell, B.B.; Starborg, M.; Brookes, S.; Peters, G. Inhibitors of cyclin-dependent kinases induce features of replicative senescence in early passage human diploid fibroblasts. Curr. Biol., 1998, 8(6), 351-354.
[http://dx.doi.org/10.1016/S0960-9822(98)70137-X] [PMID: 9512419]
[http://dx.doi.org/10.1016/S0960-9822(98)70137-X] [PMID: 9512419]
[82]
Wallace, D.C. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: A dawn for evolutionary medicine. Annu. Rev. Genet., 2005, 39, 359-407.
[http://dx.doi.org/10.1146/annurev.genet.39.110304.095751] [PMID: 16285865]
[http://dx.doi.org/10.1146/annurev.genet.39.110304.095751] [PMID: 16285865]
[83]
Botto, N.; Berti, S.; Manfredi, S.; Al-Jabri, A.; Federici, C.; Clerico, A.; Ciofini, E.; Biagini, A.; An-dreassi, M.G. Detection of mtDNA with 4977 bp deletion in blood cells and atherosclerotic lesions of pa-tients with coronary artery disease. Mutat. Res., 2005, 570(1), 81-88.
[http://dx.doi.org/10.1016/j.mrfmmm.2004.10.003] [PMID: 15680405]
[http://dx.doi.org/10.1016/j.mrfmmm.2004.10.003] [PMID: 15680405]
[84]
Costantino, S.; Camici, G.G.; Mohammed, S.A.; Volpe, M.; Lüscher, T.F.; Paneni, F. Epigenetics and cardiovascular regenerative medicine in the elderly. Int. J. Cardiol., 2018, 250, 207-214.
[http://dx.doi.org/10.1016/j.ijcard.2017.09.188] [PMID: 28988828]
[http://dx.doi.org/10.1016/j.ijcard.2017.09.188] [PMID: 28988828]
[85]
Zhou, S.; Liu, S.; Liu, X.; Zhuang, W. Bioinformatics gene analysis of potential biomarkers and ther-apeutic targets for unstable atherosclerotic plaque-related stroke. J. Mol. Neurosci., 2020.
[http://dx.doi.org/10.1007/s12031-020-01725-2] [PMID: 33155176]
[http://dx.doi.org/10.1007/s12031-020-01725-2] [PMID: 33155176]
[86]
Bibbins-Domingo, K. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. preventive services task force recommendation statement. Ann. Intern. Med., 2016, 164(12), 836-845.
[http://dx.doi.org/10.7326/M16-0577] [PMID: 27064677]
[http://dx.doi.org/10.7326/M16-0577] [PMID: 27064677]
[87]
Stone, N.J.; Robinson, J.G.; Lichtenstein, A.H.; Bairey Merz, C.N.; Blum, C.B.; Eckel, R.H.; Gold-berg, A.C.; Gordon, D.; Levy, D.; Lloyd-Jones, D.M.; McBride, P.; Schwartz, J.S.; Shero, S.T.; Smith, S.C.J., Jr; Watson, K.; Wilson, P.W.F. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American college of cardiolo-gy/American heart association task force on practice guidelines. J. Am. Coll. Cardiol., 2014, 63(25 Pt B), 2889-2934.
[http://dx.doi.org/10.1016/j.jacc.2013.11.002] [PMID: 24239923]
[http://dx.doi.org/10.1016/j.jacc.2013.11.002] [PMID: 24239923]
[88]
Powers, W.J.; Rabinstein, A.A.; Ackerson, T.; Adeoye, O.M.; Bambakidis, N.C.; Becker, K.; Biller, J.; Brown, M.; Demaerschalk, B.M.; Hoh, B.; Jauch, E.C.; Kidwell, C.S.; Leslie-Mazwi, T.M.; Ovbiagele, B.; Scott, P.A.; Sheth, K.N.; Southerland, A.M.; Summers, D.V.; Tirschwell, D.L. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke, 2018, 49(3), e46-e110.
[http://dx.doi.org/10.1161/STR.0000000000000158] [PMID: 29367334]
[http://dx.doi.org/10.1161/STR.0000000000000158] [PMID: 29367334]
[89]
Dato, S.; Crocco, P.; D’Aquila, P.; de Rango, F.; Bellizzi, D.; Rose, G.; Passarino, G. Exploring the role of genetic variability and lifestyle in oxidative stress response for healthy aging and longevity. Int. J. Mol. Sci., 2013, 14(8), 16443-16472.
[http://dx.doi.org/10.3390/ijms140816443] [PMID: 23965963]
[http://dx.doi.org/10.3390/ijms140816443] [PMID: 23965963]
[90]
Montenegro, M.F.; Neto-Neves, E.M.; Dias-Junior, C.A.; Ceron, C.S.; Castro, M.M.; Gomes, V.A.; Kanashiro, A.; Tanus-Santos, J.E. Quercetin restores plasma nitrite and nitroso species levels in renovascu-lar hypertension. Naunyn Schmiedebergs Arch. Pharmacol., 2010, 382(4), 293-301.
[http://dx.doi.org/10.1007/s00210-010-0546-1] [PMID: 20694791]
[http://dx.doi.org/10.1007/s00210-010-0546-1] [PMID: 20694791]
[91]
Patel, R.V.; Mistry, B.M.; Shinde, S.K.; Syed, R.; Singh, V.; Shin, H-S. Therapeutic potential of quercetin as a cardiovascular agent. Eur. J. Med. Chem., 2018, 155, 889-904.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.053] [PMID: 29966915]
[http://dx.doi.org/10.1016/j.ejmech.2018.06.053] [PMID: 29966915]
[92]
Santos-Parker, J.R.; Strahler, T.R.; Bassett, C.J.; Bispham, N.Z.; Chonchol, M.B.; Seals, D.R. Curcu-min older adults by increasing nitric oxide bioavailability and reducing oxidative stress. Aging-Us, 2017, 9(1), 187-208.
[http://dx.doi.org/10.18632/aging.101149] [PMID: 28070018]
[http://dx.doi.org/10.18632/aging.101149] [PMID: 28070018]
[93]
Li, J.; Zhang, C.X.; Liu, Y.M.; Chen, K.L.; Chen, G. A comparative study of anti-aging properties and mechanism: resveratrol and caloric restriction. Oncotarget, 2017, 8(39), 65717-65729.
[http://dx.doi.org/10.18632/oncotarget.20084] [PMID: 29029466]
[http://dx.doi.org/10.18632/oncotarget.20084] [PMID: 29029466]