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  • The cofilin phosphatase slingshot homolog 1 restrains angiotensin II-induced vascular hypertrophy and fibrosis in vivo.

The cofilin phosphatase slingshot homolog 1 restrains angiotensin II-induced vascular hypertrophy and fibrosis in vivo.

Laboratory investigation; a journal of technical methods and pathology (2018-10-07)
Holly C Williams, Jing Ma, Daiana Weiss, Bernard Lassègue, Roy L Sutliff, Alejandra San Martín
ABSTRACT

The dual specificity phosphatase slingshot homolog 1 (SSH1) contributes to actin remodeling by dephosphorylating and activating the actin-severing protein cofilin. The reorganization of the actin cytoskeleton has been implicated in chronic hypertension and the subsequent mechano-adaptive rearrangement of vessel wall components. Therefore, using a novel Ssh1-/- mouse model, we investigated the potential role of SSH1 in angiotensin II (Ang II)-induced hypertension, and vascular remodeling. We found that loss of SSH1 did not produce overt phenotypic changes and that baseline blood pressures as well as heart rates were comparable between Ssh1+/+ and Ssh1-/- mice. Although 14 days of Ang II treatment equally increased systolic blood pressure in both genotypes, histological assessment of aortic samples indicated that medial thickening was exacerbated by the loss of SSH1. Consequently, reverse-transcription quantitative PCR analysis of the transcripts from Ang II-infused animals confirmed increased aortic expression levels of fibronectin, and osteopontin in Ssh1-/- when compared to wild-type mice. Mechanistically, our data suggest that fibrosis in SSH1-deficient mice occurs by a process that involves aberrant responses to Ang II-induced TGFβ1. Taken together, our work indicates that Ang II-dependent fibrotic gene expression and vascular remodeling, but not the Ang II-induced pressor response, are modulated by SSH1-mediated signaling pathways and SSH1 activity is protective against Ang II-induced remodeling in the vasculature.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Actin, α-Smooth Muscle antibody, Mouse monoclonal, clone 1A4, purified from hybridoma cell culture
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid
Sigma-Aldrich
Anti-Fibronectin Antibody, Chemicon®, from rabbit