Molecular mechanisms responsible for the anti-inflammatory and protective effect of high-density lipoprotein on the endothelium

In addition to their role in reverse cholesterol transport, high-density lipoproteins (HDLs) exert several beneficial effects, including the prevention and correction of endothelial dysfunction. HDLs promote endothelium proliferation and diminish endothelial apoptosis; they play a key role in vasorelaxation by increasing the release of nitric oxide and prostacyclin through the induction of the expression and the activity of endothelial nitric oxide synthase and the coupling of cyclo-oxygenase 2 and prostacyclin synthase. In addition, HDLs affect coagulation, fibrinolysis, platelet adhesion, adhesion molecules and protease expression, and exert antioxidant activity. These effects are achieved at the gene expression level and are dependent on the activation of several intracellular signalling pathways, including PI3K/Akt, extracellular signal-regulated kinase (ERK) 1/2, protein kinase C, and p38MAPK (mitogen-activated protein kinase). The complexity of the signalling pathways modulated by HDL reflects the different effects of the components of this class of lipoproteins such as apolipoproteins or lipids on endothelial cell gene expression and the subsequent observed modulation of endothelial function. The in vivo relevance of these findings to endothelial recovery during physiological or pathological conditions remain to be addressed; nevertheless, the results of clinical studies with synthetic HDL, apolipoprotein A-I mimetics and drugs selectively affecting HDL plasma levels and biological functions that are becoming available support the importance of the correction of endothelial function by HDL. © 2007 Adis Data Information BV. All rights reserved.