Sex differences in the developmental origins of cardiovascular disease

Abstract

The Developmental Origins of Health and Disease (DOHaD) proposes that adverse events during early life program an increased risk for cardiovascular disease. Experimental models provide proof of concept but also indicate that insults during early life program sex differences in adult blood pressure and cardiovascular risk. This review will highlight the potential mechanisms that contribute to the etiology of sex differences in the developmental programming of cardiovascular disease.

FIGURE 1.

Sex differences in the developmental origins of hypertension Developmental programming of blood pressure and cardiovascular risk in the male involves testosterone-dependent activation of the renin angiotensin system. In addition, an increase in oxidative stress and the renal nerves contribute to the development and maintenance of hypertension.

FIGURE 2.

Sex differences in the developmental origins of hypertension Numerous studies indicate that the ovarian hormones contribute to sex differences in programmed cardiovascular risk. Upregulation of compensatory mechanisms, including the ACE2/AT₂R pathways and anti-oxidants, may be estrogen dependent. Yet, increases in oxidative stress may program cardiovascular risk in female offspring impacted by an insult during early life. In addition, age leads to an increase in visceral adiposity, circulating leptin, and involvement of the renal nerves in the development of age-dependent hypertension.