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Open Access Highly Accessed Research article

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

Kranthi Vemparala1, Ambuj Roy2, Vinay Kumar Bahl2, Dorairaj Prabhakaran3, Neera Nath4, Subrata Sinha5, Pradipta Nandi2, Ravindra Mohan Pandey6, Kolli Srinath Reddy7, Ajay Manhapra8 and Ramakrishnan Lakshmy1*

Author Affiliations

1 Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India

2 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India

3 Center for Chronic Disease Control and CARRS COE, Public Health Foundation of India, New Delhi, India

4 Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India

5 National Brain Research Center, Manesar, Haryana, India

6 Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India

7 Public Health Foundation of India, New Delhi, India

8 Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA

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BMC Cardiovascular Disorders 2013, 13:104  doi:10.1186/1471-2261-13-104

Published: 19 November 2013

Abstract

Background

The 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.

Methods

EPCs 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.

Result

The 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).

Conclusions

We 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.

Keywords:
Premature coronary artery disease; Endothelial progenitor cells; Senescence; Telomere length; Telomerase activity