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 high-density 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 pre-clinical 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.