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Izzo, C. Ox-Stress, Genetics-Epigenetic and Aging CVD. Encyclopedia. Available online: https://encyclopedia.pub/entry/6496 (accessed on 27 July 2024).
Izzo C. Ox-Stress, Genetics-Epigenetic and Aging CVD. Encyclopedia. Available at: https://encyclopedia.pub/entry/6496. Accessed July 27, 2024.
Izzo, Carmine. "Ox-Stress, Genetics-Epigenetic and Aging CVD" Encyclopedia, https://encyclopedia.pub/entry/6496 (accessed July 27, 2024).
Izzo, C. (2021, January 17). Ox-Stress, Genetics-Epigenetic and Aging CVD. In Encyclopedia. https://encyclopedia.pub/entry/6496
Izzo, Carmine. "Ox-Stress, Genetics-Epigenetic and Aging CVD." Encyclopedia. Web. 17 January, 2021.
Ox-Stress, Genetics-Epigenetic and Aging CVD
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Aging can be seen as process characterized by accumulation of oxidative stress induced damage. Oxidative stress derives from different endogenous and exogenous processes, all of which ultimately lead to progressive loss in tissue and organ structure and functions. The oxidative stress theory of aging expresses itself in age-related diseases. Aging is in fact a primary risk factor for many diseases and in particular for cardiovascular diseases and its derived morbidity and mortality. Here we highlight the role of oxidative stress in age-related cardiovascular aging and diseases. We take into consideration the molecular mechanisms, the structural and functional alterations, and the diseases accompanied to the cardiovascular aging process.

aging oxidative stress cardiovascular diseases molecular mechanisms genetics epigenetics

1. Introduction

In addition to being a common denominator to many chronic disease manifestations, oxidative stress-induced endothelial dysfunction is the key mechanism linking aging to increased risk of clinical cardiovascular disease and death [1]. As we age, the continuous imbalance between the generation of ROS—which increases progressively—and the ability of endogenous anti-oxidant defense mechanisms—which becomes increasingly reduced—results in reduced NO bioavailability and impaired vasodilatory function [2][3]. Longitudinal studies conducted in long-lived and very long-lived cohorts, including “centenarians” have demonstrated the undeniable role of genetic variations in the regulation of the oxidative stress response in aging [4][5][6], referred to as the capacity of triggering various regulatory processes in response to oxidative stress. Among the antioxidant enzymes, Soerensen and colleagues [7] showed that a major role in longevity seems to be attributed to manganese superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPX1), indicating that variation in these genes may affect human life span.

2. Findings and Trials

In age-related cardiovascular diseases, a prominent role of sirtuins has also been thoroughly explored. Sirtuins (Sirt) belong to class III histone deacetylases that have been associated with aging for their nicotinamide adenine dinucleotide (NAD+)-dependent enzymatic activity. Seven sirtuin family members have been identified so far, denoted as Sirt1-Sirt7, each of which displays differential subcellular localizations: Sirt1, 6, and 7 are localized in the nucleus, Sirt2 is cytosolic, Sirt3 to Sirt5 are found in the mitochondrial compartment, the major source of intracellular ROS [8]. Many existing studies have demonstrated a protective role of the sirtuins against both accelerated vascular aging and atherosclerosis [9]. For instance, Sirt1 deficiency increases oxidative stress, inflammation, and foam cell formation and induced the senescence of endothelial as well as vascular smooth muscle cells. In support of this notion, using human vascular smooth muscle cells (VSMC) isolated from donors (from 12 to 88-year-old subjects), Thompson and colleagues [10] demonstrated an inverse correlation between the endogenous Sirt1 protein expression and the donor age. In an independent study conducted in 3763 subjects, the authors showed that homozygous minor allele genotypes within rs2841505 (Sirt5) and rs107251 (Sirt6) negatively influenced survival, whereas homozygous minor allele genotypes within rs511744 (Sirt3) were associated with an increased lifespan [11]. Furthermore, while partial Sirt1 deletion in atherosclerotic mice enhanced atherogenesis [12], Sirt1 overexpression reduced atherosclerotic plaque formation in ApoE−/− mice following 10 weeks of high-fat diet feeding [13]. In an attempt to investigate the molecular mechanisms behind the role of Sirt1 in inducing lifespan expansion, deletion of Beclin 1/Autophagy protein (Atg) 6 was found to abrogate longevity in C. Elegans [14]. In fact, besides being implicated in a variety of cellular processes, including energy metabolism cell stress response and cell/tissue survival, recent studies have also identified a role for sirtuins in the regulation of autophagy, a cellular housekeeping process, which is critical for the maintenance of tissue homeostasis during aging, particularly cardiac and vascular health [15]. For example, in response to cellular stress, including caloric restriction, Sirt1 upregulated the expression and directly deacetylated several Atg proteins, including Atg7 and Atg8, thereby inducing autophagy [16]. Likewise, Sirt1-null mice have increased basal acetylation of autophagic proteins and a reduced autophagy function [17]. In addition, knockdown of Sirt1 prevented the induction of autophagy by its indirect activator resveratrol and by nutrient deprivation in human cells [18]. Acting in a distinct manner from that of Sirt1, Sirt3 also regulated autophagy both positively and negatively. In particular, it has been reported that Sirt3 overexpression activated the mammalian target of rapamycin complex 1 (mTORC1), a consistent inhibitor of autophagy. In addition, Sirt3 gene silencing promoted autophagy and protected human hepatocytes from lipotoxicity [19]. In contrast, by inducing autophagy, Sirt3 prevented ischemia-induced neuronal apoptosis in cortical neurons cells [20]. Recent findings have also reported the beneficial role for Sirt6-mediated autophagy against cardiovascular diseases [21]. Indeed, using an in vitro model, Sirt6 reduced the formation of foam cells through an autophagy-dependent pathway, thus suggesting the protective role of Sirt6 in preventing atherosclerosis [22].

The mitochondrial adaptor protein p66Shc is another key determinant of aging since its genetic deletion induces stress resistance and prolongs lifespan by 30% [23]. The mammalian SHC locus encodes for three different isoforms carrying a Src-homology 2 domain. Owing to its unique N-terminal region, p66Shc is the only protein playing a critical role in redox metabolism [24]. Genetic deletion of p66Shc has been shown to reduce the production of free radicals in the brain, improve stroke outcome, and preserve neurological function in an ischemia-reperfusion injury model [25]. In patients with acute ischemic stroke, p66Shc expression was transiently increased and correlated with short-term neurological outcome [26]. Furthermore, p66Shc has also been involved in hyperglycemia-associated changes in endothelial function. In a mouse model of streptozotocin-induced diabetes, deletion of p66Shc protein protected mice against oxidative stress-induced endothelial dysfunction as well as lipid peroxidation in aortic tissue [27].

By modulating the expression of several antioxidant enzymes, the proto-oncogene JunD has been suggested as a potential target to prevent ROS-driven age-related cardiovascular diseases; indeed, JunD knockout mice exhibited impaired endothelium-dependent relaxation and reduced life span [28]. Conversely, in vivo JunD overexpression rescued age-induced endothelial dysfunction [29]. Moreover, low levels of JunD have been reported in monocytes of old healthy subjects when compared with young individuals, and the decrease was correlated with the expression of scavenging and oxidative enzymes [30].

Bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4) has recently emerged as another molecule with important role in regulating aging and longevity. Recent studies have shown the role of a polymorphic variant in the gene encoding BPIFB4 in determining exceptional longevity in 3 independent populations [31]. In addition, homozygous carriers of the so-called longevity-associated variant (LAV)-BPIFB4 exhibited higher circulating BPIFB4 levels and increased eNOS activity in circulating mononuclear cells [32]. In line with these findings, circulating BPIFB4 levels were closely linked with the health status of long-living individuals [33]. Interestingly, LAV-BPIFB4 gene transfer decelerated frailty progression in aged mice and homozygous LAV-BPIFB4 haplotype inversely correlated with frailty in elderly subjects [34].

Growing evidence suggests microRNAs (miRNA) as critical regulators of aging and cardiovascular disease [35]. Acting at the post-transcriptional levels, these small non-coding RNA molecules are able to negatively regulate gene expression by inducing mRNA degradation or translational repression of their targets [36].

First discovered in Caenorhabditis elegans, several miRNAs have been found to both positive and negatively regulate longevity through canonical pathways during aging, including insulin signaling, heat-shock factors (HSFs), AMP-activated protein kinases (AMPKs), mitogen-activated protein kinases (MAPKs), sirtuins, target of rapamycin (TOR), and mitochondria. Because miRNAs and aging signaling pathways are conserved across species, from nematodes to humans, studies on C. Elegans have provided clues to understanding mechanisms of age-related processes. For example, it has been shown that adult-specific loss of argonaute-like gene-1 activity resulted in a shorter lifespan when compared with that of wild-type [37]. Furthermore, a loss-of-function mutation in lin-4 and gain-of-function mutants of its target lin-14 displayed a reduced lifespan, which was rescued to a significant extent by knockdown of lin-14 only during adulthood [38]. Van Almen et al. found decreased miR-18 and miR-19 levels in aged heart failure-prone mice when compared to age-matched controls [39]. Importantly, these findings were also confirmed in cardiac biopsies of idiopathic cardiomyopathy patients at old age, where decreased miR-18a, miR-19a, and miR-19b expression was associated with severe heart failure [40]. Together with increased ROS production, miR-21 was found to be upregulated in heart, liver, kidney, and aorta of spontaneous hypertensive rats (SHR). Interestingly, exposure to exogenous miR-21 was able to lower blood pressure levels in the SHR rats, indicating miRNAs as novel potential therapeutic target in hypertension [41]. Among the most studied miRNAs, circulating levels of miR-126, miR-130a, miR-142, miR-21, and miR-93 have been found to be associated with human aging . For example, miR-21 level is increased with aging process and aging associated-diseases, but its expression level decreased in individuals aged over 80 and in centenarians, suggesting the beneficial effects of low levels of miR-21 for longevity [42]. Menghini et al. found that miR-217 is widely expressed in aged but not young endothelial cells, and that its overexpression can induce endothelial cell senescence formation, thus suggesting the involvement of miR-217 in the pathogenesis of cardiovascular diseases [43]. Finally, using PCR arrays, Smith-Vikos et al. [37] identified multiple differentially expressed microRNA in serum samples from individuals who had documented lifespans from 58 to 92. Interestingly, six of these circulating miRNAs significantly correlated with subsequent longevity, suggesting that these miRNAs may serve as useful biomarkers of human aging [37].

Along with findings from several clinical trials that have failed to show long-term improvement with antioxidants [44][45], the above studies suggest the importance of directly acting on upstream signaling rather than adopting strategies to scavenge formed ROS to delay age-related disease onset.

References

  1. Brandes, R.P.; Fleming, I.; Busse, R. Endothelial aging. Res. 2005, 66, 286–294, doi:10.1016/j.cardiores.2004.12.027.
  2. Newaz, M.A.; Yousefipour, Z.; Oyekan, A. Oxidative stress-associated vascular aging is xanthine oxidase-dependent but not NAD(P)H oxidase-dependent. Cardiovasc. Pharmacol. 2006, 48, 88–94, doi:10.1097/01.fjc.0000245402.62864.0a.
  3. 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. Res. 2007, 100, 1659–1666, doi:10.1161/01.RES.0000269183.13937.e8.
  4. Paolisso, G.; Tagliamonte, M.R.; Rizzo, M.R.; Manzella, D.; Gambardella, A.; Varricchio, M. Oxidative stress and advancing age: Results in healthy centenarians. Am. Geriatr. Soc. 1998, 46, 833–838, doi:10.1111/j.1532-5415.1998.tb02716.x.
  5. Suzuki, M.; Willcox, D.C.; Rosenbaum, M.W.; Willcox, B.J. Oxidative stress and longevity in okinawa: An investigation of blood lipid peroxidation and tocopherol in okinawan centenarians. Gerontol. Geriatr. Res. 2010, 2010, 380460, doi:10.1155/2010/380460.
  6. Soerensen, M.; Christensen, K.; Stevnsner, T.; Christiansen, L. The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old. Ageing Dev. 2009, 130, 308–314, doi:10.1016/j.mad.2009.01.005.
  7. Schiattarella, G.G.; Hill, J.A. Metabolic control and oxidative stress in pathological cardiac remodelling. Heart J. 2017, 38, 1399–1401, doi:10.1093/eurheartj/ehw199.
  8. Laina, A.; Stellos, K.; Stamatelopoulos, K. Vascular ageing: Underlying mechanisms and clinical implications. Gerontol. 2018, 109, 16–30, doi:10.1016/j.exger.2017.06.007.
  9. Mattagajasingh, I.; Kim, C.S.; Naqvi, A.; Yamamori, T.; Hoffman, T.A.; Jung, S.B.; DeRicco, J.; Kasuno, K.; Irani, K. SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Natl. Acad. Sci. USA 2007, 104, 14855–14860, doi:10.1073/pnas.0704329104.
  10. Donato, A.J.; Magerko, K.A.; Lawson, B.R.; Durrant, J.R.; Lesniewski, L.A.; Seals, D.R. SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans. Physiol. 2011, 589, 4545–4554, doi:10.1113/jphysiol.2011.211219.
  11. Zarzuelo, M.J.; Lopez-Sepulveda, R.; Sanchez, M.; Romero, M.; Gomez-Guzman, M.; Ungvary, Z.; Perez-Vizcaino, F.; Jimenez, R.; Duarte, J. SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: Implications for vascular aging. Pharmacol. 2013, 85, 1288–1296, doi:10.1016/j.bcp.2013.02.015.
  12. Ota, H.; Akishita, M.; Eto, M.; Iijima, K.; Kaneki, M.; Ouchi, Y. Sirt1 modulates premature senescence-like phenotype in human endothelial cells. Mol. Cell. Cardiol. 2007, 43, 571–579, doi:10.1016/j.yjmcc.2007.08.008.
  13. Luo, J.; Nikolaev, A.Y.; Imai, S.; Chen, D.; Su, F.; Shiloh, A.; Guarente, L.; Gu, W. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 2001, 107, 137–148, doi:10.1016/s0092-8674(01)00524-4.
  14. Thompson, A.M.; Wagner, R.; Rzucidlo, E.M. Age-related loss of SirT1 expression results in dysregulated human vascular smooth muscle cell function. J. Physiol. Heart Circ. Physiol. 2014, 307, 533–541, doi:10.1152/ajpheart.00871.2013.
  15. TenNapel, M.J.; Lynch, C.F.; Burns, T.L.; Wallace, R.; Smith, B.J.; Button, A.; Domann, F.E. SIRT6 minor allele genotype is associated with >5-year decrease in lifespan in an aged cohort. PLoS ONE 2014, 9, e115616, doi:10.1371/journal.pone.0115616.
  16. Stein, S.; Lohmann, C.; Schafer, N.; Hofmann, J.; Rohrer, L.; Besler, C.; Rothgiesser, K.M.; Becher, B.; Hottiger, M.O.; Boren, J.; et al. SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis. Heart J. 2010, 31, 2301–2309, doi:10.1093/eurheartj/ehq107.
  17. Zhang, Q.J.; Wang, Z.; Chen, H.Z.; Zhou, S.; Zheng, W.; Liu, G.; Wei, Y.S.; Cai, H.; Liu, D.P.; Liang, C.C. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Res. 2008, 80, 191–199, doi:10.1093/cvr/cvn224.
  18. Morselli, E.; Maiuri, M.C.; Markaki, M.; Megalou, E.; Pasparaki, A.; Palikaras, K.; Criollo, A.; Galluzzi, L.; Malik, S.A.; Vitale, I.; et al. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis. 2010, 1, e10, doi:10.1038/cddis.2009.8.
  19. Lee, I.H.; Yun, J.; Finkel, T. The emerging links between sirtuins and autophagy. Methods Mol. Biol 2013, 1077, 259–271, doi:10.1007/978-1-62703-637-5_17.
  20. Lee, I.H.; Cao, L.; Mostoslavsky, R.; Lombard, D.B.; Liu, J.; Bruns, N.E.; Tsokos, M.; Alt, F.W.; Finkel, T. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Natl. Acad. Sci. USA 2008, 105, 3374–3379, doi:10.1073/pnas.0712145105.
  21. Li, S.; Dou, X.; Ning, H.; Song, Q.; Wei, W.; Zhang, X.; Shen, C.; Li, J.; Sun, C.; Song, Z. Sirtuin 3 acts as a negative regulator of autophagy dictating hepatocyte susceptibility to lipotoxicity. Hepatology 2017, 66, 936–952, doi:10.1002/hep.29229.
  22. Dai, S.H.; Chen, T.; Li, X.; Yue, K.Y.; Luo, P.; Yang, L.K.; Zhu, J.; Wang, Y.H.; Fei, Z.; Jiang, X.F. Sirt3 confers protection against neuronal ischemia by inducing autophagy: Involvement of the AMPK-mTOR pathway. Free Radic. Biol. Med. 2017, 108, 345–353, doi:10.1016/j.freeradbiomed.2017.04.005.
  23. He, J.; Zhang, G.; Pang, Q.; Yu, C.; Xiong, J.; Zhu, J.; Chen, F. SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition. FEBS J. 2017, 284, 1324–1337, doi:10.1111/febs.14055.
  24. Migliaccio, E.; Giorgio, M.; Mele, S.; Pelicci, G.; Reboldi, P.; Pandolfi, P.P.; Lanfrancone, L.; Pelicci, P.G. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 1999, 402, 309–313, doi:10.1038/46311.
  25. Spescha, R.D.; Shi, Y.; Wegener, S.; Keller, S.; Weber, B.; Wyss, M.M.; Lauinger, N.; Tabatabai, G.; Paneni, F.; Cosentino, F.; et al. Deletion of the ageing gene p66(Shc) reduces early stroke size following ischaemia/reperfusion brain injury. Heart J. 2013, 34, 96–103, doi:10.1093/eurheartj/ehs331.
  26. Spescha, R.D.; Klohs, J.; Semerano, A.; Giacalone, G.; Derungs, R.S.; Reiner, M.F.; Rodriguez Gutierrez, D.; Mendez-Carmona, N.; Glanzmann, M.; Savarese, G.; et al. Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke. Heart J. 2015, 36, 1590–1600, doi:10.1093/eurheartj/ehv140.
  27. Camici, G.G.; Schiavoni, M.; Francia, P.; Bachschmid, M.; Martin-Padura, I.; Hersberger, M.; Tanner, F.C.; Pelicci, P.; Volpe, M.; Anversa, P.; et al. Genetic deletion of p66(Shc) adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress. Natl. Acad. Sci. USA 2007, 104, 5217–5222, doi:10.1073/pnas.0609656104.
  28. Paneni, F.; Osto, E.; Costantino, S.; Mateescu, B.; Briand, S.; Coppolino, G.; Perna, E.; Mocharla, P.; Akhmedov, A.; Kubant, R.; et al. Deletion of the activated protein-1 transcription factor JunD induces oxidative stress and accelerates age-related endothelial dysfunction. Circulation 2013, 127, 1229–1240, doi:10.1161/CIRCULATIONAHA.112.000826.
  29. Laurent, G.; Solari, F.; Mateescu, B.; Karaca, M.; Castel, J.; Bourachot, B.; Magnan, C.; Billaud, M.; Mechta-Grigoriou, F. Oxidative stress contributes to aging by enhancing pancreatic angiogenesis and insulin signaling. Cell Metab. 2008, 7, 113–124, doi:10.1016/j.cmet.2007.12.010.
  30. Villa, F.; Carrizzo, A.; Spinelli, C.C.; Ferrario, A.; Malovini, A.; Maciag, A.; Damato, A.; Auricchio, A.; Spinetti, G.; Sangalli, E.; et al. Genetic Analysis Reveals a Longevity-Associated Protein Modulating Endothelial Function and Angiogenesis. Res. 2015, 117, 333–345, doi:10.1161/CIRCRESAHA.117.305875.
  31. Villa, F.; Malovini, A.; Carrizzo, A.; Spinelli, C.C.; Ferrario, A.; Maciag, A.; Madonna, M.; Bellazzi, R.; Milanesi, L.; Vecchione, C.; et al. Serum BPIFB4 levels classify health status in long-living individuals. Ageing 2015, 12, 27, doi:10.1186/s12979-015-0054-8.
  32. Malavolta, M.; Dato, S.; Villa, F.; Rango, F.; Iannone, F.; Ferrario, A.; Maciag, A.; Ciaglia, E.; D’Amato, A.; Carrizzo, A.; et al. LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice. Aging (Albany NY) 2019, 11, 6555–6568, doi:10.18632/aging.102209.
  33. Smith-Vikos, T.; Liu, Z.; Parsons, C.; Gorospe, M.; Ferrucci, L.; Gill, T.M.; Slack, F.J. A serum miRNA profile of human longevity: Findings from the Baltimore Longitudinal Study of Aging (BLSA). Aging (Albany NY) 2016, 8, 2971–2987, doi:10.18632/aging.101106.
  34. Quiat, D.; Olson, E.N. MicroRNAs in cardiovascular disease: From pathogenesis to prevention and treatment. Clin. Investig. 2013, 123, 11–18, doi:10.1172/JCI62876.
  35. Kinser, H.E.; Pincus, Z. MicroRNAs as modulators of longevity and the aging process. Genet. 2020, 139, 291–308, doi:10.1007/s00439-019-02046-0.
  36. Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116, 281–297, doi:10.1016/s0092-8674(04)00045-5.
  37. Smith-Vikos, T.; Slack, F.J. MicroRNAs and their roles in aging. Cell Sci. 2012, 125, 7–17, doi:10.1242/jcs.099200.
  38. Kato, M.; Chen, X.; Inukai, S.; Zhao, H.; Slack, F.J. Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans. RNA 2011, 17, 1804–1820, doi:10.1261/rna.2714411.
  39. Boehm, M.; Slack, F. A developmental timing microRNA and its target regulate life span in C. elegans. Science 2005, 310, 1954–1957, doi:10.1126/science.1115596.
  40. van Almen, G.C.; Verhesen, W.; van Leeuwen, R.E.; van de Vrie, M.; Eurlings, C.; Schellings, M.W.; Swinnen, M.; Cleutjens, J.P.; van Zandvoort, M.A.; Heymans, S.; et al. MicroRNA-18 and microRNA-19 regulate CTGF and TSP-1 expression in age-related heart failure. Aging Cell 2011, 10, 769–779, doi:10.1111/j.1474-9726.2011.00714.x.
  41. Li, H.; Zhang, X.; Wang, F.; Zhou, L.; Yin, Z.; Fan, J.; Nie, X.; Wang, P.; Fu, X.D.; Chen, C.; et al. MicroRNA-21 Lowers Blood Pressure in Spontaneous Hypertensive Rats by Upregulating Mitochondrial Translation. Circulation 2016, 134, 734–751, doi:10.1161/CIRCULATIONAHA.116.023926.
  42. Olivieri, F.; Capri, M.; Bonafe, M.; Morsiani, C.; Jung, H.J.; Spazzafumo, L.; Vina, J.; Suh, Y. Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging. Ageing Dev. 2017, 165, 162–170, doi:10.1016/j.mad.2016.12.004.
  43. Menghini, R.; Casagrande, V.; Cardellini, M.; Martelli, E.; Terrinoni, A.; Amati, F.; Vasa-Nicotera, M.; Ippoliti, A.; Novelli, G.; Melino, G.; et al. MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation 2009, 120, 1524–1532, doi:10.1161/CIRCULATIONAHA.109.864629.
  44. Drummond, G.R.; Selemidis, S.; Griendling, K.K.; Sobey, C.G. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Rev. Drug Discov. 2011, 10, 453–471, doi:10.1038/nrd3403.
  45. Morris, C.D.; Carson, S. Routine vitamin supplementation to prevent cardiovascular disease: A summary of the evidence for the U.S. Preventive Services Task Force. Intern. Med. 2003, 139, 56–70, doi:10.7326/0003-4819-139-1-200307010-00014.
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