Local Renin-Angiotensin System Signaling Mediates Cellular Function of Aortic Valves

Area of Science:

• Cardiovascular Biology
• Biomaterials Science
• Cellular Physiology

Background:

• The renin-angiotensin system (RAS) is implicated in aortic valve disease pathogenesis.
• The specific functional effects of RAS mediators on valve interstitial cells (VICs) remain largely uncharacterized.

Purpose of the Study:

• To investigate the role of RAS mediators and inhibitors in regulating VIC contractility.
• To develop and utilize a novel gelatin-based valve thin film (vTF) platform for studying VIC function.

Main Methods:

• VICs were cultured under quiescent, activated, and osteogenic conditions on gelatin vTF.
• Cell phenotype, morphology, and contractility were assessed.
• VICs were treated with angiotensin I, angiotensin II, ACE inhibitors, and AT1R inhibitors.

Main Results:

• Anisotropic VIC alignment on vTF was achieved irrespective of culture conditions.
• VICs in activated and osteogenic media exhibited enhanced elongation and increased α-SMA expression.
• Angiotensin I and Ang II dose-dependently increased VIC contractile stress.
• ACE and AT1R inhibitors significantly reduced VIC contraction.

Conclusions:

• A local RAS is active within VICs, influencing their contractile function.
• The developed vTF platform is a promising tool for screening drugs targeting valve disease.
• These findings offer insights into potential therapeutic strategies for aortic valve disease.