Angiotensin (1-7) decreases the fibrotic process by modulating the TGF-β1/AKT pathway in rat corpus cavernosum smooth muscle cells

Background: Hyperglycemia induces the development of cavernosa atherosclerosis and fibrosis, and transforming growth factor-β1 (TGF-β1) plays an important role in the induction, promoting fibrosis in corporal tissue, which replaces the normal corpora cavernosa with fibrotic tissue.

Aim: This study explored the role of Angiotensin (1-7) (Ang 1-7) and the regulatory mechanism underlying fibrosis in the corpora cavernosa.

Methods: Primary rat corpus cavernosum smooth muscle cells (CCSMCs) were cultured under normal and high glucose (HG) with or without Ang 1-7. The protein levels of TGF-β1, Collagen I, TGF-β receptor-I (TβRI), and caveolin-1 (Cav-1) were evaluated by western blotting. Reactive Oxygen Species (ROS) and peroxynitrite (ONOO^-) levels in Cell Culture supernatants were measured by enzyme-linked immunosorbent assay. Intracellular calcium content was determined by flow cytometry.

Outcomes: High glucose significantly increased the protein levels of TGF-β1 and Collagen I, triggered oxidative stress, modulated the Akt signaling pathway, and elevated intracellular calcium ion levels in CCSMCs. Angiotensin (1-7) treatment significantly attenuated HG-induced adverse effects in CCSMCs.

Results: The protective effects of Ang 1-7 against fibrosis in HG-exposed CCSMCs were associated with the downregulation of TGF-β1 levels, accompanied by the attenuation of oxidative stress. The Ang1-7-induced effects in CCSMC cells are mediated through the inhibition of the TGF-β1/Akt signaling pathway.

Clinical translation: Our studies provide new insights into the critical role of the TGF-β1/Akt signaling pathway in CCSMCs, identifying it as a potential therapeutic target for treating patients with erectile dysfunction.

Strengths and limitations: Angiotensin (1-7) is a unique peptide of the renin-angiotensin system with substantial therapeutic potential. This study assessed the therapeutic effect of Ang 1-7 on the fibrotic process and provided new insights for clinical applications. The clinical formulation, drug stability, and in vivo bioactivity of Ang-1-7 remain to be fully investigated.

Conclusion: Angiotensin (1-7) exerts a protective effect on CCSMCs under HG conditions by modulating the TGF-β1/Akt signaling pathway.

Angiotensin (1-7); TGF-β1; calcium ion levels; diabetes mellitus; fibrosis; oxidative stress.