Remnant like particles may induce atherosclerosis via accelerating endothelial progenitor cells senescence.
Remnant like particles (RLPs) are closely associated with coronary heart disease, whereas the underlying mechanisms are complex and have not been fully elucidated. Studies show that maintenance of endothelial cells layer is essential for normal function of vessel. Endothelial progenitor cells (EPCs) were shown to incorporate into sites of neovascularization and home to sites of endothelial denudation, thus provide an endogenous repair mechanism. Risk factors of coronary heart disease can impair EPCs repairing function by inducing EPCs senescence. EPCs senescence is associated with telomerase inactivation, which is regulated via phosphatidylinositol-3-kinase/Akt kinase (PI3K/Akt) signaling pathway. RLPs are triglyceride rich lipoproteins reflecting chylomicron remnants and very-low-density lipoprotein remnants. RLPs can impair endothelial function via inhibiting endothelial NO synthase (eNOS) activity and nitric oxide (NO) production by inducing intracellular oxidant levels. However, there is no research about effect of RLPs on EPCs. Evidence shows that RLPs can induce focal adhesion kinase (FAK) activation in monocytic U937 cells. Therefore, it can be hypothesized that RLPs could inhibit eNOS and telomerase activities, thus induce atherosclerosis by promoting EPCs senescence via FAK and its downstream PI3K/Akt pathway through an oxidative mechanism.
Pu
Da-Rong
DR
Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China.
Liu
Ling
L
D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology*; D016922:Cellular Senescence / Q000502:physiology*; D002784:Cholesterol / Q000009:adverse effects* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D008074:Lipoproteins / Q000009:adverse effects* / Q000502:physiology*; D013234:Stem Cells / Q000473:pathology*; D014280:Triglycerides / Q000009:adverse effects* / Q000502:physiology*
D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol