Atherogenesis: hyperhomocysteinemia interactions with LDL, macrophage function, paraoxonase 1, and exercise

Despite great strides in understanding the atherogenesis process, the mechanisms are not entirely known. In addition to diet, cigarette smoking, genetic predisposition, and hypertension, hyperhomocysteinemia (HHcy), an accumulation of the noncoding sulfur-containing amino acid homocysteine (Hcy), is a significant contributor to atherogenesis. Although exercise decreases HHcy and increases longevity, the complete mechanism is unclear. In light of recent evidence, in this review, we focus on the effects of HHcy on macrophage function, differentiation, and polarization. Though there is need for further evidence, it is most likely that HHcy-mediated alterations in macrophage function are important contributors to atherogenesis, and HHcy-countering strategies, such as nutrition and exercise, should be included in the combinatorial regimens for effective prevention and regression of atherosclerotic plaques. Therefore, we also included a discussion on the effects of exercise on the HHcy-mediated atherogenic process.