17β-Estradiol promotes sex-specific dysfunction in isolated human arterioles

Area of Science:

• Cardiovascular Biology
• Endocrinology
• Vascular Physiology

Background:

• Estrogen is considered vasculoprotective in large arteries, but its role in the microvasculature and cardiovascular disease (CVD) risk is unclear.
• Microvascular dysfunction independently predicts adverse cardiac events, yet human microvessel responses to estrogen are understudied.
• Hormone therapy and estrogen exposure increase CVD risk in cis- and trans-females, suggesting complex vascular effects.

Purpose of the Study:

• To investigate the effects of chronic 17β-estradiol exposure on human microvascular function.
• To examine sex-specific differences in microvascular response to estrogen.
• To determine the role of estrogen receptor expression in mediating these effects.

Main Methods:

• Isolated human arterioles from females (<40 and ≥40 yr) and males were chronically exposed to 17β-estradiol.
• Vascular reactivity, including nitric oxide (NO)-mediated dilation, was assessed.
• Estrogen receptor (ER-α, ER-β) and G protein-coupled estrogen receptor (GPER) expression in arterioles was analyzed.

Main Results:

• Chronic estrogen exposure impaired NO-mediated dilation in arterioles from adult females of all ages.
• Estrogen induced both endothelial and smooth muscle dysfunction in arterioles from males.
• Females <40 yr showed higher ER-β and GPER expression in the endothelium compared to older females and males.

Conclusions:

• Contrary to large artery effects, chronic estrogen exposure is detrimental to human microvascular function.
• Sex-specific differences in microvascular response and estrogen receptor expression exist.
• These findings may explain increased CVD risk associated with estrogen use in females.