Endothelial dysfunction after androgen deprivation therapy and the possible underlying mechanisms

Area of Science:

• Cardiovascular Research
• Endocrinology
• Urology

Background:

• Androgen deprivation therapy (ADT) is crucial for prostate cancer (PCa) management.
• ADT is associated with increased cardiovascular risks, including heart attack and stroke.
• Understanding ADT's cardiovascular impact is vital for preventive strategies.

Purpose of the Study:

• To investigate the pathophysiological mechanisms linking ADT to cardiovascular risk.
• To compare the cardiovascular effects of different ADT modalities in a rat model.

Main Methods:

• Male rats underwent bilateral orchidectomy (Orx), LHRH agonist (leuprolide), or LHRH antagonist (degarelix) treatment for 24 weeks.
• Vascular function was assessed via reactivity assays.
• Protein and mRNA levels of key pathways (e.g., AT1R, NOX2) were analyzed using immunohistochemistry and qPCR.

Main Results:

• All ADT groups exhibited endothelial dysfunction in aorta, renal, and coronary arteries.
• The LHRH agonist (leuprolide) group showed greater aortic and intrarenal endothelial impairment compared to the antagonist.
• Upregulation of the Angiotensin II-AT1R-NOX2 pathway and increased oxidative stress were observed in ADT groups.

Conclusions:

• ADT induces endothelial dysfunction in male rats.
• LHRH agonists appear to pose a greater cardiovascular risk than antagonists.
• The AngII-AT1R-NOX2 pathway and oxidative stress mediate ADT-induced cardiovascular complications.