Submitted on January 23, 2007
Revised on May 11, 2007
Accepted on May 12, 2007
Remnant-like lipoprotein particles impair endothelial function: Direct and indirect effects on nitric oxide synthase
Xiaoyan Zheng and Ling Liu
Department of Cardiology, the Second Xiangya Hospital ,Central South University, Changsha, Hunan 410011
Corresponding Author: feliuling{at}medmail.com.cn
Remnant-like lipoprotein particles (RLPs) have been implicated as potentially atherogenic lipoproteins. Endothelial dysfunction is known to be an early event in atherosclerosis and an important contributor to the pathogenesis of coronary artery disease. Moreover, there is considerable evidence linking increased RLPs cholesterol levels with endothelial dysfunction, reflected by impaired endothelial vasodilatation and abnormal endothelial secretion. The underlying mechanisms by which RLPs may contribute to endothelial dysfunction are complex and have not been completely elucidated. Since the expression and activation of endothelial nitric oxide synthase (eNOS) are vital to endothelial function, and recent data have implied an association between RLPs and eNOS, this manuscript proposed the hypothesis that RLPs could impair endothelial function via direct and indirect effects on eNOS: 1) RLPs may affect the autophosphorylation of focal adhesion kinase and its downstream phosphatidylinositol kinase/Akt (protein kinase B) signaling pathway, resulting in eNOS inactivation through inducing intracellular oxidative stress in endothelial cells. 2) RLPs could affect the expression or activation of eNOS indirectly by stimulating secretion of various inflammatory factors from multiple origins. The practical applications of this manuscript provide new insights for the future investigation of RLPs.
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