Telomeres and Telomerase in Cardiovascular Diseases.
Telomeres are tandem repeat DNA sequences present at the ends of each eukaryotic chromosome to stabilize the genome structure integrity. Telomere lengths progressively shorten with each cell division. Inflammation and oxidative stress, which are implicated as major mechanisms underlying cardiovascular diseases, increase the rate of telomere shortening and lead to cellular senescence. In clinical studies, cardiovascular risk factors such as smoking, obesity, sedentary lifestyle, and hypertension have been associated with short leukocyte telomere length. In addition, low telomerase activity and short leukocyte telomere length have been observed in atherosclerotic plaque and associated with plaque instability, thus stroke or acute myocardial infarction. The aging myocardium with telomere shortening and accumulation of senescent cells limits the tissue regenerative capacity, contributing to systolic or diastolic heart failure. In addition, patients with ion-channel defects might have genetic imbalance caused by oxidative stress-related accelerated telomere shortening, which may subsequently cause sudden cardiac death. Telomere length can serve as a marker for the biological status of previous cell divisions and DNA damage with inflammation and oxidative stress. It can be integrated into current risk prediction and stratification models for cardiovascular diseases and can be used in precise personalized treatments. In this review, we summarize the current understanding of telomeres and telomerase in the aging process and their association with cardiovascular diseases. In addition, we discuss therapeutic interventions targeting the telomere system in cardiovascular disease treatments.
Department of Cardiology, Chang Gung Memorial Hospital, 33305 Taoyuan, Taiwan. potential.ya@gmail.com.
Jih-Kai
JK
Yeh
Department of Cardiology, Chang Gung Memorial Hospital, 33305 Taoyuan, Taiwan. cwang@ocean.ag.|Chang Gung University College of Medicine, 33302 Taoyuan, Taiwan. cwang@ocean.ag.
Chao-Yung
CY
Wang
cardiovascular diseases; cell senescence; telomere and telomerase