Sex Differences in Inflammation during Atherosclerosis

Atherosclerosis is the leading cause of death in the United States and worldwide, yet more men die from atherosclerosis than women, and at a younger age. Women, on the other hand, mainly develop atherosclerosis following menopause, and particularly if they have one or more autoimmune diseases, suggesting that the immune mechanisms that increase disease in men are different from those in women. The key processes in the pathogenesis of atherosclerosis are vascular inflammation, lipid accumulation, intimal thickening and fibrosis, remodeling, and plaque rupture or erosion leading to myocardial infarction and ischemia. Evidence indicates that sex hormones alter the immune response during atherosclerosis, resulting in different disease phenotypes according to sex. Women, for example, respond to infection and damage with increased antibody and autoantibody responses, while men have elevated innate immune activation. This review describes current knowledge regarding sex differences in the inflammatory immune response during atherosclerosis. Understanding sex differences is critical for improving individualized medicine.