Lipid-Induced Modulation of Protective Signalling Pathways in Cardiovascular Disease: The Role of High Density Lipoproteins

Richard      W. James; Miguel      A. Frias; Sandrine      Lecour

doi:10.2174/157436212800376627

Abstract

High density lipoproteins have a well-established, negative correlation with risk of cardiovascular disease. There is currently particular interest in trying to exploit this relationship by raising serum high density lipoprotein cholesterol to lower risk. More recent studies suggest that high density lipoproteins have a more widespread impact on cardiovascular pathophysiology, beyond its involvement in cholesterol metabolism. The lipoprotein influences the functioning of endothelial cells and cardiomyocytes in a manner suggesting a protective effect under conditions of physiological stress. On-going studies are investigating the magnitude of the influence of the lipoprotein on cell function, notably be defining the signalling pathways that are involved. Advances in this area will be discussed in the following review. These studies may identify new avenues that can be explored as potential targets to treat cardiovascular disease. A logical extension is to consider the high density lipoprotein complex itself as a potential therapeutic. In this respect the ability to synthesise artificial high density lipoproteins with functional properties of the native lipoprotein complex is a particularly attractive option. Such studies have already been initiated, as will be discussed below.

Keywords: Apolipoprotein AI; cardiomyocyte; endothelium; HDL; ischemia-reperfusion injury; sphingosine-1-phosphate; SAFE pathway