Fatty acid modulation of atherosclerosis by peroxisome proliferator-activated receptors

摘要

While atherosclerosis is a major killer, there is now concern that mortality from the disease will increase due to the rising incidence of type II diabetes. Because diet can potentially influence both diseases, it is important to elucidate the roleof diet in the progression of atherosclerosis. In addition, the mechanisms involved in dietary-related alterations of the disease need to be defined to guide public health recommendations to reduce atherosclerosis incidence and limiting unwanted side effects. Since diet is thought to play a role in atherosclerosis even without added complications due to type II diabetes, reducing the incidence of that metabolic disease will not be enough. While evidence is increasing that high intake of carbohydrate canlead to type II diabetes and atherosclerosis, the preponderance of existing evidence indicates that intake of specific fats as a major dietary causal factor. It has recently been hypothesized that a dietary fat link to atherosclerosis may depend partlyon the activity of a transeriptional regulator, the peroxisome proliferator activated receptors (PPAR). Thusfar, PPAR a, beta/delta and gamma, have been shown to play a major role in metabolism, inflammation, and cancer. Furthermore, PPAR may regulate specific processes associated with atherosclerosis such as triglyceride and low density lipoprotein (LDL) metabolism; the reverse cholesterol transport pathway; lipid accumulation within plaques; the local inflammatory response and plaque stability. Synthetic ligands for PPAR have been developed; however, natural ligands include specific fatty acids and their metabolites. Though the role of PPAR in atherosclerosis has been reported with respect to synthetic ligands, additional studies need to be done withestablished and possible natural ligands. In this review, we will focus on the relation of dietary fat to PPAR alteration of atherosclerosis.