Feasibility of Lecithin: Cholesterol Acyltransferase as the Therapeutic Target of Atherosclerosis.

Abstract

Atherosclerosis is a global concern in this century. It is a progressive disease caused by the accumulation of cholesterol plaque, which thickens and hardens the arterial walls. It was found that low-density lipoprotein is the major leading factor because it delivers cholesterol towards the arterial walls. By contrast, high-density lipoprotein has anti-atherogenic properties due to its ability to remove cholesterol for hepatic excretion. Lecithin: cholesterol acyltransferase is an endogenous enzyme that boosts highdensity lipoprotein-mediated reverse cholesterol transport. It has thereby been studied as a therapeutic target of atherosclerosis for decades. Currently, different lecithin: cholesterol acyltransferase-based therapies have different progress under development. This review illustrated the structural, biochemical, and functional properties of this enzyme. The basic rationale for two main types of this enzyme-based therapy, enzyme replacement and gene therapy, was also explained. Enzyme replacement involves artificial recombinant human lecithin: cholesterol acyltransferase. Gene therapy utilises adeno-associated viral vectors to allow enzyme expression in vivo. In addition, the advantages and limitations of each treatment were also evaluated by summarising clinical and preclinical data. Although whether reverse cholesterol transport is the route by which lecithin: cholesterol acyltransferase achieves its anti-atherogenic effects is not clear yet, and the variety of safety issues of the techniques, this enzyme is still a promising therapeutic target for further pre-clinical and clinical efforts.