Assessment of female sex in preclinical vascular models

Cardiovascular disease remains the leading cause of death worldwide, with sequelae of atherosclerosis contributing significantly to patient morbidity and mortality. A number of sex differences in the pathophysiology of atherosclerosis and in the outcomes after procedures performed for atherosclerotic complications have been documented in humans; however, despite women accounting for half the number of participants in clinical trials supported by the National Institutes of Health, there are very few preclinical studies that include female animals. Animal models of atherosclerosis, ischemia, angioplasty, aneurysms, and venous remodeling have focused on sex hormones as drivers of sex-specific disease outcomes. Estrogens appear to play a protective role in decreasing atherosclerosis, vessel response to injury, and aneurysm formation through modulation of the cellular response to hypoxia and injury, lipid metabolism, inflammatory responses, modulation of the extracellular matrix, and decreased oxidative stress. While androgens contribute to positive vessel remodeling, such as seen during arteriovenous fistula maturation, they are also responsible for increased proteolysis, leading to an increased rate of aneurysm formation.