Inhibition of Smooth Muscle β-Catenin Hinders Neointima Formation After Vascular Injury

• DOI: 10.1161/atvbaha.116.308643
• Publication Date: 2017-03-17T01:10:36Z
• Authors: Dario F. Riascos-...; Prameladevi Chinn...; Jordana N. Gross; Vanessa Almonte; Lander Egaña-Gorroño; Dippal Parikh; Smitha Jayakumar; Liang Guo; Nicholas E.S. Sib...
• Keywords: Neointima

Objective— Smooth muscle cells (SMCs) contribute to neointima formation after vascular injury. Although β-catenin expression is induced injury, whether its function essential in SMCs for neointimal growth unknown. Moreover, although inhibitors of have been developed, their effects on SMC not tested. We assessed the requirement short-term homeostasis and response arterial injury investigated growth. Approach Results— used an inducible, conditional genetic deletion adult mice. Uninjured arteries from mice lacking were indistinguishable controls terms structure marker gene expression. After carotid artery ligation, however, vessels developed smaller neointimas, with lower cell proliferation increased apoptosis. showed decreased mRNA Mmp2 , Mmp9 Sphk1 S1pr1 (genes that promote formation), higher levels Jag1 Gja1 inhibit protein secretion, reduced invasion vitro. PKF118-310 ICG-001 limited mouse human a dose-dependent manner. Conclusions— dispensable maintenance state differentiation uninjured arteries, but required Pharmacological hinder SMCs. Thus, inhibiting has potential as therapy limit accumulation obstruction.