Early accelerated senescence of circulating endothelial progenitor cells in premature coronary artery disease patients in a developing country - a case control study

Abstract

BackgroundThe decreased number and senescence of circulating endothelial progenitor cells (EPCs) are considered markers of vascular senescence associated with aging, atherosclerosis, and coronary artery disease (CAD) in elderly. In this study, we explore the role of vascular senescence in premature CAD (PCAD) in a developing country by comparing the numerical status and senescence of circulating EPCs in PCAD patients to controls.MethodsEPCs were measured by flow cytometry in 57 patients with angiographically documented CAD, and 57 controls without evidence of CAD, recruited from random patients ≤ 50 years of age at All India Institute of Medical Sciences. EPC senescence as determined by telomere length (EPC-TL) and telomerase activity (EPC-TA) was studied by real time polymerase chain reaction (q PCR) and PCR– ELISA respectively.ResultThe number of EPCs (0.18% Vs. 0.039% of total WBCs, p < 0.0001), and EPC-TL (3.83 Vs. 5.10 kb/genome, p = 0.009) were markedly lower in PCAD patients compared to controls. These differences persisted after adjustment for age, sex, BMI, smoking and medications. EPC-TA was reduced in PCAD patients, but was statistically significant only after adjustment for confounding factors (1.81 Vs. 2.20 IU/cell, unadjusted p = 0.057, adjusted p = 0.044).ConclusionsWe observed an association between increased vascular cell senescence with PCAD in a sample of young patients from India. This suggests that early accelerated vascular cell senescence may play an important mechanistic role in CAD epidemic in developing countries like India where PCAD burden is markedly higher compared to developed countries.

Oxidative stress and inflammation: Early predictive indicators of multiple recurrent coronary in‐stent chronic total occlusions in elderly patients after coronary stenting

“…Our findings revealed that the levels of EPC, SDF‐1α, VEGF, and NO were decreased greatly in the elderly patients with multivessel reocclusions compared to the elderly patients with one‐ or two‐vessel reocclusions. Oxidative stress responses and inflammatory responses decreased the overexpressions of EPC, SDF‐1α, VEGF, and NO, and the reduced circulating EPC, SDF‐1α, VEGF, and NO led to coronary in‐stent restenosis . The present study suggested that the decreased levels of EPC, SDF‐1α, VEGF, and NO were related to coronary in‐stent reocclusion and severity of reocclusion after coronary stenting and may be considered as the important targets for treatment in a new stent design for interventional therapy of coronary artery stenoses.…”

“…The enhanced oxidative stress shortened EPC telomeres and decreased EPC telomerase activity and promoted the reduced circulating EPCs in the patients with CHD. The research suggested that the significantly lower EPC number led to endothelial dysfunction and atherosclerosis in the patients with CHD . The studies also showed that the insufficient numbers of EPCs were related to coronary stenosis and severity of CHD, and the number of circulating EPCs was significantly lower in two and three vessel disease compared to single vessel disease in the patients with CHD.…”

“…Dysfunctions of EPCs and vascular endothelium played the important roles in the pathophysiology of coronary heart disease (CHD) and coronary arteriosclerosis progression. Decreased telomere length of EPCs was also related to CHD in elderly patients . In the patients with CHD, the decreases in the number and activities of EPCs and the functional impairment of circulating EPCs were associated with the severity of coronary stenosis in CHD patients.…”

Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes

“…31 Consistent with this view, several studies have used LTL as a marker of biological aging and have linked it to age-related diseases including atherosclerosis and its consequences, 32 such as peripheral vascular disease, 7, 33 CAD, 34 and importantly, cardiovascular mortality. 2, 32 Since aging is associated with decline in circulating PCs, and atherosclerosis is thought to develop as a result of an imbalance between endogenous repair mechanisms and factors causing cell injury, 35, 36 most of the studies have speculated that these observed clinical associations were related to decreased regenerative capacity. Increased inflammation and oxidative stress, two known key factors in the pathophysiology of atherosclerosis, 37 may result in increased utilization of circulating PCs, which home to the ischemic tissue and denuded endothelium to contribute to vascular and endothelial repair.…”

Longitudinal Telomere Erosion in Lymphocyte Subsets of Patients with Atherosclerotic Peripheral Arterial Disease (PAD)

“…In patients with CAD significant telomere attrition can already be found in early stages of disease [14]. The difference in the telomere length attrition between PAD and CAD may also result from a much lower cellular turnover by the chronic inflammation of PAD compared to a much higher cellular turnover in CAD.…”