Sex Differences in the Immune System in Relation to Hypertension and Vascular Disease

Abstract

Hypertension is the leading risk factor for cardiovascular disease and mortality worldwide. Despite intensive research into the mechanisms underlying the development of hypertension, it remains difficult to control blood pressure in a large proportion of patients. Young men have a higher prevalence of hypertension compared with age-matched women, and this holds true until approximately the fifth decade of life. Following the onset of menopause, the incidence of hypertension among women begins to surpass that of men. The immune system has been demonstrated to play a role in the pathophysiology of hypertension, and biological sex and sex hormones can affect the function of innate and adaptive immune cell populations. Recent studies in male and female animal models of hypertension have begun to unravel the relationship among sex, immunity, and hypertension. Hypertensive male animals show a bias toward proinflammatory T-cell subsets, including interleukin (IL) 17-producing T_H17 cells, and increased renal infiltration of T cells and inflammatory macrophages. Conversely, premenopausal female animals are largely protected from hypertension, and have a predilection for anti-inflammatory T regulatory cells and production of anti-inflammatory cytokines, such as IL-10. Menopause abrogates female protection from hypertension, which may be due to changes among anti-inflammatory T regulatory cell populations. Since development of novel treatments for hypertension has plateaued, determining the role of sex in the pathophysiology of hypertension may open new therapeutic avenues for both men and women.