出版社：American Society for Biochemistry and Molecular Biology
摘要：Remnant-like lipoprotein particles (RLPs) have been implicatedas potentially atherogenic lipoproteins. Endothelial dysfunctionis known to be an early event in atherosclerosis and an importantcontributor to the pathogenesis of coronary artery disease.Moreover, there is considerable evidence linking increased RLPcholesterol levels with endothelial dysfunction, reflected byimpaired endothelial vasodilatation and abnormal endothelialsecretion. The underlying mechanisms by which RLPs may contributeto endothelial dysfunction are complex and have not been completelyelucidated. Because the expression and activation of endothelialnitric oxide synthase (eNOS) are vital to endothelial function,and recent data have implied an association between RLPs andeNOS, this manuscript proposes the hypothesis that RLPs couldimpair endothelial function via direct and indirect effectson eNOS: RLPs may affect the autophosphorylation of focal adhesionkinase and its downstream phosphatidylinositol kinase/Akt (proteinkinase B) signaling pathway, resulting in eNOS inactivationthrough induction of intracellular oxidative stress in endothelialcells; and RLPs could affect the expression or activation ofeNOS indirectly by stimulating secretion of various inflammatoryfactors from multiple origins. The practical applications ofthis manuscript provide new insights for the future investigationof RLPs.Supplementary key words endothelial dysfunction • atherosclerosis • inflammation
Abbreviations: ACh, acetylcholine; apoE, apolipoprotein E; CAD, coronary artery disease; CRP, C-reactive protein; EDR, endothelium-dependent vasorelaxation; eNOS, endothelial nitric oxide synthase; FAK, focal adhesion kinase; FMD, flow-mediated endothelium-dependent dilatation; HUVEC, human umbilical vein endothelial cell; ICAM-1, intercellular adhesion molecule-1; IL-1, interleukin-1; NO, nitric oxide; Ox-LDL, oxidized LDL; RLP, remnant-like lipoprotein particle; RLP-C, RLP-cholesterol; TNF-, tumor necrosis factor-; VCAM-1, vascular cell adhesion molecule-1
, tumor necrosis factor-
