Polyunsaturated Fatty Acids and Atherosclerosis: Insights from Pre-Clinical Studies

Abstract

Atherosclerosis and its complications are responsible for more global deaths than any other disease. Atherosclerosis is a chronic inflammatory disease of medium and large arteries that can cause clinical complications such as myocardial infarction and cerebrovascular accidents. Current therapies against atherosclerosis mainly target the dyslipidemia associated with the disease and are associated with considerable residual risk for cardiovascular disease together with various side effects. In addition, the outcomes of clinical trials on many pharmaceutical agents against promising therapeutic targets have been disappointing. This has resulted in considerable recent interest on nutraceuticals in the prevention of atherosclerosis and as add-on with current pharmaceutical therapies. However, nutraceutical research has considerably lagged those on pharmaceuticals on two key aspects, large clinical trials and mechanistic insights. The latter forms the focus of this review in relation to the potential beneficial actions of polyunsaturated fatty acids as identified from pre-clinical studies. Practical Applications: There is substantial recent interest in the use of nutraceuticals for the prevention and treatment of atherosclerosis. It is therefore important that the molecular mechanisms underlying their protective actions are fully understood and large clinical trials are carried out to evaluate their efficacy. Polyunsaturated fatty acids represent promising anti-atherogenic agents. This review illuminates on the mechanisms underlying their actions in relation to atherosclerosis as revealed from pre-clinical studies using in vitro and in vivo model systems. Atherosclerosis is an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease. Current therapies against atherosclerosis are not fully effective and the outcomes on many promising pharmaceutical agents have been disappointing. This has generated substantial interest in nutraceuticals such as polyunsaturated fatty acids (PUFAs) in the prevention and treatment of this disease. This review describes the actions of omega-3 and -6 PUFAs on key cellular processes associated with atherosclerosis in vitro and the development of the disease in mouse model systems in vivo together with the mechanisms underlying their beneficial effects and studies in humans.