Vascular Disease Risk in Patients With Hypertriglyceridemia: Endothelial Progenitor Cells, Oxidative Stress, Accelerated Senescence, and Impaired Vascular Repair

Abstract

Arterial wall repair largely depends on the integrity of both the adult endothelial cells (ECs) lining the lumen of the arteries and the circulating endothelial progenitor cells (EPCs). Lifelong EC turnover is likely the main mechanism of repair replacing damaged and senescent ECs. It is believed, however, that EPCs can be recruited at sites of vascular injury including atherosclerotic plaques to hasten repair. Bacterial chromosomes are round, protecting them from damage at chromosome ends during division. The ends of linear chromosomes, as found in eukaryotes (including in humans), are subject to damage during chromosome duplication associated with mitosis. Telomeres are regions of repeated DNA sequences at chromosome ends that protect eukaryotic chromosomes from such damage. With aging, turnover of ECs and EPCs associated with telomere shortening signals for senescence when telomeres cannot shorten further (Fig. 1). In addition, risk factors for cardiovascular disease (CVD), on the one hand, accelerate EC and EPC turnover and can, on the other hand, promote stress-induced senescence (SIS) independently of telomere shortening by inducing DNA damage. Telomerases are enzymes that add DNA sequence repeats to the end of telomeres to replace bits of telomere DNA that are lost during chromosome copying accompanying cell division. Telomerase activity can therefore compensate telomere shortening by re-elongating telomeres, although its DNA polymerase activity is limited in somatic cells. Telomerase activity is, however, highly sensitive to oxidative stress associated with risk factors for CVD in ECs, thereby limiting its efficacy. Furthermore, telomerase increasingly appears as a sensor of DNA damage; its exportation from the nucleus to the cytosol signals for SIS.