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


RESULTS
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.
Kranthi
K
Vemparala
Ambuj
A
Roy
Vinay Kumar
VK
Bahl
Dorairaj
D
Prabhakaran
Neera
N
Nath
Subrata
S
Sinha
Pradipta
P
Nandi
Ravindra Mohan
RM
Pandey
Kolli Srinath
KS
Reddy
Ajay
A
Manhapra
Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India. rlakshmy@aiims.ac.in.
Ramakrishnan
R
Lakshmy
D000328:Adult; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000502:physiology*; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000453:epidemiology* / Q000503:physiopathology; D003906:Developing Countries; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors