The role of HDL and phospholipids in endothelial cellular senescence

Abstract

High-density lipoproteins (HDLs) are commonly recognized as antiatherogenic molecules; these possess anti-inflammatory properties and participate in the production of Nitric Oxide (NO) by endothelial cells. In addition, critical patients characterized by a dropdown of HDL-cholesterol plasma levels during the acute phase, have an increased risk of intrahospital death. The molecular mechanisms underlying the beneficial effects of HDL are not well understood. However, current clinical evidence suggests a relationship between HDL and cellular senescence, a stress response characterized by a mostly irreversible loss in the replicative potential of the cell. This permanent cell cycle arrest can be induced through a variety of stimuli including telomere shortening, oxidative stress, DNA damage and oncogenic signals. At the organismal level, senescence contributes to aging and has been associated with numerous age-related pathologies. Now, few studies have documented that cellular senescence exhibits an alteration in lipid composition, leading to morphological changes in membrane remodeling. Additionally, a relationship between the altered expression of regulatory genes of lipid metabolism and senescent cells has been recently uncovered. Therefore, here we aimed to analyze the role of HDLs in endothelial cell senescence induced by doxorubicin and hydrogen peroxide. The results reveal that there is a possible impact of HDL on the onset of cellular senescence, although this may be more associated with membrane homeostasis, as reflected in a decrease in the number of cells positive for the senescence marker SA-β-galactosidase, as well as a decrease in apoptosis associated with the stress generated by the senescence inducer. However, further study of these lipoproteins in senescent cells is needed. Likewise, this study opens the door to consider hydrogen peroxide as a strong candidate to induce senescence in HMEC-1 endothelial cells derived from the oxidative stress that these cells can encounter physiologically.