Related Experiment Video
Updated: Aug 12, 2025
Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
Androgen aggravates aortic aneurysms via suppressing PD-1 in mice
Insights
Androgens contribute to aortic aneurysms in males by suppressing PD-1 expression in T cells. Restoring PD-1 with anti-PD-1 therapy may impact aneurysm development.
Area of Science:
- Cardiovascular Science
- Immunology
- Endocrinology
Background:
- Aortic aneurysms disproportionately affect men, with androgens implicated but molecular mechanisms unclear.
- Understanding androgen's role in cardiovascular disease sexual dimorphism is critical for targeted therapies.
Approach:
- Investigated the role of androgens and androgen receptors (AR) in aldosterone-salt-induced aortic aneurysms in mice.
- Identified T cells expressing programmed cell death protein 1 (PD-1) as a key mediator.
- Utilized anti-PD-1 antibody treatment in orchiectomized mice to assess its impact.
Key Points:
- Male mice, but not female, developed aortic aneurysms under aldosterone-salt conditions.
- Androgen and AR signaling were essential for this sex-specific response.
- Androgen receptor (AR) directly suppresses PD-1 expression in T cells within the spleen.
Conclusions:
- Androgen promotes aortic aneurysms by suppressing T cell PD-1 expression, revealing a novel molecular pathway.
- This finding suggests potential implications for cancer patients undergoing immune checkpoint therapy and at risk for aortic aneurysms.
Abstract:
Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms, a devastating vascular disease with a higher prevalence and mortality rate in men than women. However, the molecular mechanism by which androgen mediates aortic aneurysms is largely unknown. Here, we report that male but not female mice develop aortic aneurysms in response to aldosterone and high salt (Aldo-salt). We demonstrate that both androgen and androgen receptors (AR) are crucial for the sexually dimorphic response to Aldo-salt. We identify T cells expressing programmed cell death protein 1 (PD-1), an immune checkpoint molecule important in immunity and cancer immunotherapy, as a key link between androgen and aortic aneurysms. We show that intraperitoneal injection of anti-PD-1 antibody reinstates Aldo-salt-induced aortic aneurysms in orchiectomized mice. Mechanistically, we demonstrate that AR binds to the PD-1 promoter to suppress its expression in the spleen. Hence, our study reveals an important but unexplored mechanism by which androgen contributes to aortic aneurysms by suppressing PD-1 expression in T cells. Our study also suggests that cancer patients predisposed to the risk factors of aortic aneurysms may be advised to screen for aortic aneurysms during immune checkpoint therapy.
