Ramin Zargham1, Gaétan Thibault. 1. Institut de recherches cliniques de Montréal (IRCM), Université de Montréal and McGill University, 110 avenue des pins ouest, Montréal, Québec, Canada H2W 1R7.
Abstract
OBJECTIVE: Migration of vascular smooth muscle cells (VSMCs) from the tunica media to the intima is a key event in neointima formation after coronary artery angioplasty. The central dogma in VSMC migration is cell modulation from the contractile to the noncontractile phenotype. Increased alpha8beta1 integrin expression, observed in situations where the majority of cells are in the contractile phenotype, led us to hypothesize that a decrease of alpha8beta1 integrin may play an important role in the migratory state of VSMCs. METHODS AND RESULTS: To test this hypothesis, neointima formation was induced in the left common carotid artery of adult male Sprague-Dawley rats by balloon dilatation. Immunohistochemical and Western blotting analysis showed reduced expression for up to 4 weeks of both the alpha8 and beta1 integrin subunits as well as smooth muscle alpha-actin in the tunica media following balloon injury. Moreover, ex vivo culture of carotid VSMCs revealed diminished alpha8 integrin expression in the platelet-derived growth-factor-dependent migratory state with an increase in the angiotensin-II-induced contractile state. To ascertain the functional role of alpha8 integrin in VSMC migration and proliferation, alpha8 gene expression was reduced by nearly 70% by short interference RNA (siRNA). Decreased alpha8 expression resulted in a significant increase of carotid VSMC migration but not of proliferation. CONCLUSIONS: Our results are consistent with those of other studies demonstrating that alpha8 integrin could be used as an appropriate differentiation marker. In addition, depressed alpha8 integrin expression (after vascular injury or siRNA knockdown) was correlated with heightened cell migratory activity, demonstrating its potential role in neointima formation.
OBJECTIVE: Migration of vascular smooth muscle cells (VSMCs) from the tunica media to the intima is a key event in neointima formation after coronary artery angioplasty. The central dogma in VSMC migration is cell modulation from the contractile to the noncontractile phenotype. Increased alpha8beta1 integrin expression, observed in situations where the majority of cells are in the contractile phenotype, led us to hypothesize that a decrease of alpha8beta1 integrin may play an important role in the migratory state of VSMCs. METHODS AND RESULTS: To test this hypothesis, neointima formation was induced in the left common carotid artery of adult male Sprague-Dawley rats by balloon dilatation. Immunohistochemical and Western blotting analysis showed reduced expression for up to 4 weeks of both the alpha8 and beta1 integrin subunits as well as smooth muscle alpha-actin in the tunica media following balloon injury. Moreover, ex vivo culture of carotid VSMCs revealed diminished alpha8 integrin expression in the platelet-derived growth-factor-dependent migratory state with an increase in the angiotensin-II-induced contractile state. To ascertain the functional role of alpha8 integrin in VSMC migration and proliferation, alpha8 gene expression was reduced by nearly 70% by short interference RNA (siRNA). Decreased alpha8 expression resulted in a significant increase of carotid VSMC migration but not of proliferation. CONCLUSIONS: Our results are consistent with those of other studies demonstrating that alpha8 integrin could be used as an appropriate differentiation marker. In addition, depressed alpha8 integrin expression (after vascular injury or siRNA knockdown) was correlated with heightened cell migratory activity, demonstrating its potential role in neointima formation.
Authors: Susan E Zimmerman; Chitkale Hiremath; Jun Tsunezumi; Zhufeng Yang; Bronwyn Finney; Denise K Marciano Journal: J Am Soc Nephrol Date: 2018-01-15 Impact factor: 10.121