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
    • "Cardiovascular diseases are connected to a premature aging phenotype [15]. Vascular endothelial cells seem to be strongly affected by aging, as endothelial cells from iliac, thoracic, and coronary arteries show age-dependent telomere shortening [16] [17] [18]. "
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    ABSTRACT: Aging is a major factor predisposing for multiple diseases. Telomeres at the ends of chromosomes protect the integrity of chromosomal DNA. A specialized six protein complex termed shelterin protects the telomere from unwanted interaction with DNA damage pathways. The aim of our study was to evaluate the integrity of telomeres and the stability of telomere protection during aging in endothelial cells (EC). We describe that aging EC can be characterized by an increased cell size (40%, p=0.02) and increased expression of PAI 1 (4 fold, p=0.02), MCP1 (10 fold, p=0.001) and GMCSF (15 fold, p=0.004). Telomeric state in aging cells is defined by an increased telomere oxidation (27%, p=0.01), reduced telomere length (62%, p=0.02) and increased DNA damage foci formation (5% in young EC versus 16% in aged EC, p=0.003). This telomeric dysfunction is accompanied by a reduction in the shelterin component TRF1 (33% mRNA, p=0.001; 24% protein, p=0.007). Overexpression of TRF1 in aging EC reduced telomere associated DNA damage foci to 5% (p=0.02) and reduces expression levels of MCP1 (18% reduction, p=0.008). Aged EC have increased telomere damage and an intrinsic loss of telomere protection. Reestablishing telomere integrity could therefore be a target for rejuvenating endothelial cell function.
    No preview · Article · Dec 2015 · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
    • "Telomeres and telomerase provide protection against threats to the genome that arise from aninherent difficulty in the asymmetric replication of DNA (Calado and Young, 2009). Recently, telomere and telomerase have been recognized as potential factors involved in the initiation and progression of cardiovascular disease (Samani and van der Harst, 2008; Fuster and Andres, 2006; Edo and Andres, 2005; Wong et al., 2008). There is accumulating evidence that connect telomere length with cardiovascular-related phenotypes, including atherosclerosis and heart failure (Wong et al., 2009). "
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    ABSTRACT: Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric Acid-Reactive Species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period.
    No preview · Article · Nov 2015 · Toxicology Letters
    • "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]. "

    No preview · Article · Jan 2015 · International Journal of Cardiology
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