In addition to their role in reverse cholesterol transport, high-density lipoprotein (HDL) exerts several beneficial effects, including the prevention and correction of endothelial dysfunction. HDL promotes proliferation of the endothelium and decreases endothelial apoptosis; it plays a key role in vasorelaxation by increasing the release of nitric oxide and prostacyclin through inducing the expression and activity of endothelial nitric oxide synthase and the coupling of cyclo-oxygenase 2 and prostacyclin synthase. In addition, HDL affects coagulation, fibrynolisis, platelet adhesion, expression of adhesion molecules and protease, and exerts anti-oxidant activity. These effects are achieved at the gene expression level and are dependent upon the activation of several intracellular signaling pathways, including PI3 kinase/Akt, extracellular signal-related kinase 1/2, protein kinase C (PKC) and p38 mitogen-activated protein kinase. The complexity of the signaling 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 modulation of endothelial function observed. The in vivo relevance of these findings to endothelial recovery during physiological or pathological conditions remains 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
HDL and endothelial function: from molecular mechanisms to clinical observations / G.D. Norata, S. Raselli, A.L. Catapano. - In: FUTURE LIPIDOLOGY. - ISSN 1746-0875. - 1:3(2006), pp. 343-355. [10.2217/17460875.1.3.343]
HDL and endothelial function: from molecular mechanisms to clinical observations
G.D. NorataPrimo
;S. RaselliSecondo
;A.L. CatapanoUltimo
2006
Abstract
In addition to their role in reverse cholesterol transport, high-density lipoprotein (HDL) exerts several beneficial effects, including the prevention and correction of endothelial dysfunction. HDL promotes proliferation of the endothelium and decreases endothelial apoptosis; it plays a key role in vasorelaxation by increasing the release of nitric oxide and prostacyclin through inducing the expression and activity of endothelial nitric oxide synthase and the coupling of cyclo-oxygenase 2 and prostacyclin synthase. In addition, HDL affects coagulation, fibrynolisis, platelet adhesion, expression of adhesion molecules and protease, and exerts anti-oxidant activity. These effects are achieved at the gene expression level and are dependent upon the activation of several intracellular signaling pathways, including PI3 kinase/Akt, extracellular signal-related kinase 1/2, protein kinase C (PKC) and p38 mitogen-activated protein kinase. The complexity of the signaling 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 modulation of endothelial function observed. The in vivo relevance of these findings to endothelial recovery during physiological or pathological conditions remains 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 HDLPubblicazioni consigliate
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