Androgen receptor (AR) in cardiovascular diseases

Abstract

Cardiovascular diseases (CVDs) are still the highest leading cause of death worldwide. Several risk factors have been linked to CVDs, including smoking, diabetes, hyperlipidemia, and gender among others. Sex hormones, especially the androgen and its receptor, androgen receptor (AR), have been linked to many diseases with a clear gender difference. Here, we summarize androgen/AR effects on CVDs, including hypertension, stroke, atherosclerosis, abdominal aortic aneurysm (AAA), myocardial hypertrophy, and heart failure, as well as metabolic syndrome/diabetes and their impacts on CVDs. Androgen/AR signaling exacerbates hypertension and anti-androgens may suppress hypertension. Androgen/AR signaling plays dual roles in strokes, depending on different kinds of factors, but generally males have a higher incidence of strokes than females. Androgen and AR differentially modulate atherosclerosis. Androgen deficiency causes elevated lipid accumulation to enhance atherosclerosis, but targeting AR in selective cells without altering serum androgen levels would suppress atherosclerosis progression. Androgen/AR signaling is crucial in AAA development and progression, and targeting androgen/AR profoundly restricts AAA progression. Men have increased cardiac hypertrophy as compared to age-matched women that may be due to androgens. Finally, androgen/AR plays important roles in contributing to obesity and insulin/leptin resistance to increase the metabolic syndrome.

Risks of Serious Toxicities from Intermittent versus Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer: A Population Based Study

“…24 Studies have shown that testosterone receptors in cardiomyocytes can induce the release of intracellular calcium in cardiomyocytes and, as a result, testosterone deficiency can lower the contractile function of the myocardium. 25–27 Our findings may be due to interruption of the cardiometabolic and vascular derangement that is hypothesized to occur with intermittent but not with continuous administration of ADT.…”

Comprehensive review of cardiovascular toxicity of drugs and related agents

“…In addition, androgenic anabolic steroids are commonly administered with other drugs such as β 2 ‐mimetics, illicit sympathomimetics, diuretics, and/or psychoactive drugs . Data on testosterone's effects on the cardiovascular system are mixed and they differ from those elicited by supraphysiologic doses of synthetic androgens . Thus, it is not easy to decipher the cardiovascular impact of anabolic androgenic steroid abuse.…”

“…Indeed, cardiac pathology is commonly observed in young people who died while abusing androgens . Other effects of anabolic androgenic steroid abuse include a small increase in arterial blood pressure, which is expected due to the known physiological difference between men and women . The cause can be increased sodium and water retention, or effects on red blood cell proliferation through increased expression of erythropoietin.…”

“…171,205 Data on testosterone's effects on the cardiovascular system are mixed and they differ from those elicited by supraphysiologic doses of synthetic androgens. 206,207 Thus, it is not easy to decipher the cardiovascular impact of anabolic androgenic steroid abuse. The basis of their abuse is to increase lean striated muscle mass.…”

“…205,211 Other effects of anabolic androgenic steroid abuse include a small increase in arterial blood pressure, which is expected due to the known physiological difference between men and women. 207,209 The cause can be increased sodium and water retention, or effects on red blood cell proliferation through increased expression of erythropoietin. Data also suggest facilitated vasoconstriction due to endogenous mediators.…”