Telomere biology and cardiovascular disease

Laboratory of Vascular Biology, Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia, C/Jaime Roig 11, 46010 Valencia, Spain.
Circulation Research (Impact Factor: 11.02). 12/2006; 99(11):1167-80. DOI: 10.1161/01.RES.0000251281.00845.18
Source: PubMed


Accumulation of cellular damage with advancing age leads to atherothrombosis and associated cardiovascular disease. Ageing is also characterized by shortening of the DNA component of telomeres, the specialized genetic segments located at the end of eukaryotic chromosomes that protect them from end-to-end fusions. By inducing genomic instability, replicative senescence and apoptosis, shortening of the telomeric DNA is thought to contribute to organismal ageing. In this Review, we discuss experimental and human studies that have linked telomeres and associated proteins to several factors which influence cardiovascular risk (eg, estrogens, oxidative stress, hypertension, diabetes, and psychological stress), as well as to neovascularization and the pathogenesis of atherosclerosis and heart disease. Two chief questions that remain unanswered are whether telomere shortening is cause or consequence of cardiovascular disease, and whether therapies targeting the telomere may find application in treating these disorders (eg, cell "telomerization" to engineer blood vessels of clinical value for bypass surgery, and to facilitate cell-based myocardial regeneration strategies). Given that most research to date has focused on the role of telomerase, it is also of up most importance to investigate whether alterations in additional telomere-associated proteins may contribute to the pathogenesis of cardiovascular disease.

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Available from: Jose Javier Fuster,
    • "Many systems of the human body are affected by aging, including: the autonomic nervous system (ANS), which can be assessed noninvasively by heart rate variability (HRV) [2] [3] [4]; cellular structures, such as telomere length [5] [6]; and mechanisms of regulation of the inflammatory process, which can be evaluated by inflammatory markers [7] [8] such as high-sensitivity C-reactive protein (hsCRP). It is known that HRV can be affected by the hsCRP [9] and that oxidative stress and inflammation processes accelerate telomere attrition [10]. "

    International Journal of Cardiology 01/2015; 178. DOI:10.1016/j.ijcard.2014.10.123 · 4.04 Impact Factor
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    • "Early diagnostics of cardiovascular disease might help to improve currently available therapies and develop new more efficient treatment strategies. The proposed mechanisms which are responsible for cardiac aging involve genetic and environmental factors, such as a decrease in telomerase activity and shortening of the DNA of the telomeres (Fuster and Andres 2006; Kajstura et al. 2006), increased oxidative stress (Terman and Brunk 2006), loss of mitochondrial function (Dai and Rabinovitch 2009) and impaired autophagy (Terman et al. 2007). In the last decade epigenetic regulators, such as small noncoding RNAs, called.g. microRNAs (miRs), were shown to be involved in cellular aging processes (Li et al. 2009; Williams et al. 2007). "
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    ABSTRACT: MicroRNAs (miRs) are small non- coding RNA molecules controlling a plethora of biological processes such as development, cellular survival and senescence. We here determined miRs differentially regulated during cardiac postnatal development and aging. Cardiac function, morphology and miR expression profiles were determined in neonatal, 4 weeks, 6 months and 19 months old normotensive male healthy C57/Bl6N mice. MiR-22 was most prominently upregulated during cardiac aging. Cardiac expression of its bioinformatically predicted target mimecan (osteoglycin, OGN) was gradually decreased with advanced age. Luciferase reporter assays validated mimecan as a bona fide miR-22 target. Both, miR-22 and its target mimecan were co- expressed in cardiac fibroblasts and smooth muscle cells. Functionally, miR-22 overexpression induced cellular senescence and promoted migratory activity of cardiac fibroblasts. Small interference RNA-mediated silencing of mimecan in cardiac fibroblasts mimicked the miR-22-mediated effects. Rescue experiments revealed that the effects of miR-22 on cardiac fibroblasts were only partially mediated by mimecan. In conclusion, miR-22 upregulation in the aging heart contributed at least partly to accelerated cardiac fibroblast senescence and increased migratory activity. Our results suggest an involvement of miR-22 in age-associated cardiac changes, such as cardiac fibrosis. Electronic supplementary material The online version of this article (doi:10.1007/s11357-012-9407-9) contains supplementary material, which is available to authorized users.
    Age 04/2012; 35(3). DOI:10.1007/s11357-012-9407-9 · 3.45 Impact Factor
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    • "Several studies have linked a short LTL to increased risks of cardiovascular disease (CVD) (Aviv, 2002; Edo and Andres, 2005; Fitzpatrick et al., 2007; Fuster and Andres, 2006) and other age-related diseases (Jeanclos et al., 1998; Valdes et al., 2010; Yaffe et al., 2009). A short LTL has also been associated with risk factors for CVD, such as cigarette smoking, obesity, and inflammation (McGrath et al., 2007; Valdes et al., 2005). "
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    ABSTRACT: Leukocyte telomere length (LTL) is linked to cardiovascular disease (CVD); however, it is unclear if LTL has an etiologic role in CVD. To gain insight into the LTL and CVD relationship, a cohort study of CVD mortality and single nucleotide polymorphisms (SNPs) in OBFC1 and TERC, genes related to LTL, was conducted among 3271 Caucasian participants ages ≥65 years enrolled 1989-1990 in the Cardiovascular Health Study. Leukocyte DNA was genotyped for SNPs in OBFC1 (rs4387287 and rs9419958) and TERC (rs3772190) that were previously associated with LTL through genome-wide association studies. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The OBFC1 SNPs were in linkage disequilibrium (r(2)=0.99), and both SNPs were similarly associated with CVD mortality in women. For women, there was a decreased risk of CVD death associated with the minor allele (rs4387287), HR=0.7; 95% CI: 0.5-0.9 (CC vs. AC) and HR=0.5; 95% CI: 0.20-1.4 (CC vs. AA) (P-trend <0.01). For men there was no association, HR=1.0; 95% CI: 0.7-1.3 (CC vs. AC) and HR=1.7; 95% CI: 0.8-3.6 (CC vs. AA) (P-trend=0.64). These findings support the hypothesis that telomere biology and associated genes may play a role in CVD-related death, particularly among women.
    Mechanisms of ageing and development 03/2012; 133(5):275-81. DOI:10.1016/j.mad.2012.03.002 · 3.40 Impact Factor
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