Caveolin‐1 as a Potential Regulator of Transforming Growth Factor‐β and Angiotensin II Type 1 Receptor Signaling in Primary Human Aortic Smooth Muscle Cells

Abstract

Vascular smooth muscle cell (VSMC) dysfunction is implicated in cardiovascular disease and can be attributed to dysregulation of Angiotensin-II (Ang-II) and transforming growth factor-β (TGF-β) signaling cascades. Despite research interest, the crosstalk and regulation between these two pathways has yet to be elucidated. Caveolin-1 (Cav-1), a structural protein within caveolae lipid rafts, affects VSMC function and structure through regulating both TGF-β and Ang-II type 1 receptor (AT1R) pathways, by inhibiting the former and stimulating the latter. However, little is known about the potential role Cav-1 may play in regulating the crosstalk between TGF-β and Ang-II pathways in VSMCs. This study investigates Cav-1 as a potential crosstalk regulator between TGF-β and AT1R signaling using primary human aortic VSMCs. Cells were treated with TGF-β in a time and dose-dependent manner. Cell lysates were subjected to western blot analysis measuring AT1R, Smad2/3, phosphorylated Smad2/3, and Cav-1 proteins. We observed down-regulation of total AT1R and Smad2/3 protein expression, and an increase in Smad2/3 phosphorylation in response to TGF-β, while, total Cav-1 protein expression remained unaltered. These findings provide new insight into possible crosstalk between TGF-β and AT1R pathways in VSMCs, and the role that Cav-1 may play. We hope this study opens new avenues in the exploration of more effective therapeutic targets in order to normalize VSMC function and structure in patients with vascular disorders. This work was funded by the Graduate Research Fund and the Office of Research and Sponsored Programs at MWU.