Acute aortic dissection (AAD) is a life-threatening cardiovascular emergency, which is closely related to the vascular smooth muscle cells (VSMCs) phenotypic switching and extracellular matrix (ECM) degradation. Previous studies have found that the secreted extracellular glycoprotein Follistatin-like 1 (FSTL1) is demonstrated as a protective factor for cardiovascular diseases. However, the role of FSTL1 in AAD remains elusive. We aimed to investigate whether FSTL1 could regulate VSMCs phenotypic switching and ECM degradation in AAD. Firstly, we found that FSTL1 expression in aorta was significantly decreased in human AAD examined by western blot and immunohistochemical staining. Then we established a mouse AAD model by administering β-aminopropionitrile (BAPN) dissolved in drinking water for 28 days. We found that FSTL1 expression in aorta was also decreased in mouse AAD. Exogenous supplement with recombinant human FSTL1 protein could rescue VSMCs phenotypic switching and ECM degradation to reduce the occurrence and progression of mouse AAD. In vitro, FSTL1 protein and adenovirus overexpressing FSTL1 (ad-FSTL1) reversed the primary VSMCs phenotypic switching and decreased the expression of MMP2 induced by PDGF-BB. Knocking down FSTL1 initiates VSMCs phenotypic switching and increases the expression of MMP2. In terms of mechanisms, AMPK phosphorylation was decreased and could be improved by FSTL1 protein in mouse AAD. FSTL1 protein and ad-FSTL1 reversed the decreased AMPK phosphorylation induced by PDGF-BB in primary VSMCs. These findings indicate that FSTL1 protects against VSMCs phenotypic switching and ECM degradation in AAD, and targeting FSTL1 may be a potential new strategy for prevention and treatment of AAD.
Keywords: AMP-activated protein kinase; Acute aortic dissection; Extracellular matrix degradation; Follistain-like protein 1; Phenotypic switching; Vascular smooth muscle cell.
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