Study On The Changes Of Telomere Length And Its Mechanism In Peripheral Blood Leukocytes Of Patients With Early - Onset Coronary Heart Disease

Background:Telomeres are repetitive, noncoding DNA sequences located at both ends of each chromosome and could protect the chromosome ends from fusing with each other. Leukocyte telomere length (LTL) has been regarded as a potential marker of biologic aging because it usually shortens in a predictable way with age.Recently, a growing interest in the relationship between coronary atherosclerotic heart disease(CHD) and cardiovascular aging has led to a number of new studies investigating LTL in various diseases. Indeed,epidemiological studies have suggested that age-dependent telomere shortening could be used as a marker for coronary heart disease. However, association does not prove causality,and it is necessary to do further research to elucidate these complicated relationships and the mechanism within them.Premature coronary artery disease (pCAD), diagnosis at less than55years of age for men and65years of age for women, appears to have particularly strong genetic components. With pCAD in this study will help to elucidate the genetic mechanisms of CHD.The understanding of cardiovascular aging and telomere biology may open up new avenues for interventions, such as stem cell therapy or agents that could retard this aging process over and beyond conventional risk factor control.Objective:To investigate clinical features, leukocyte telomere length,the level of reactive oxygen species(ROS) and total antioxidant capacity(TEAC) in patients with pCAD and to investigate the role of oxidative stress and leukocyte telomere length in CHD.Method:Eligible patients with CHD were reviewed and clinical and biochemical informations were recorded.Blood samples were obtained from patients and controls. Leukocyte telomere length were determined by Real-time quantity PCR, ROS were determined by enzyme linked immune-sorbent assay and total antioxidant capacity were determined by ABTS method.Results:Compared with non-pCAD patients, the patients with pCAD had a significantly higher rate of smoking, dyslipidemia and positive family history of CHD, but a lower Gensini Score of coronary angiography and a lower rate of heart failure during hospitalization. Compared with the healthy controls, the patients with pCAD have shorter LTL and lower total antioxidant capacity.In both patients and controls,LTL shortens with age,ROS rises with age and the ratio of TEAC to ROS decreases with age. Regression analysis showed that LTL of patients with pCAD shortens with diabetes status and decline of TEAC/ROS ratio, however the shortening of LTL of controls is only associated with elevated ROS levels independently.Conclusions:The clinical features of pCAD patients were very different from the non-pCAD patients. Compared with the healthy controls, obvious decline of TEAC and imbalance of oxidative stress and antioxidant capacity may play an important role in accelerating the attrition of telomere in pCAD patients.