β3 integrin in cardiac fibroblast is critical for extracellular matrix accumulation during pressure overload hypertrophy in mouseβ3整合素在心脏成纤维细胞对细胞外基质堆积至关重要压力过载肥大鼠标.pdf

b3 Integrin in Cardiac Fibroblast Is Critical for Extracellular Matrix Accumulation during Pressure Overload Hypertrophy in Mouse 1 1 1 1 Sundaravadivel Balasubramanian , Lakeya Quinones , Harinath Kasiganesan , Yuhua Zhang , 1 1 1,2 1,2 Dorea L. Pleasant , Kamala P. Sundararaj , Michael R. Zile , Amy D. Bradshaw , Dhandapani Kuppuswamy1* 1 Cardiology Division, Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, South Carolina, United States of America, 2 Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina, United States of America Abstract The adhesion receptor b3 integrin regulates diverse cellular functions in various tissues. As b3 integrin has been implicated in extracellular matrix (ECM) remodeling, we sought to explore the role of b3 integrin in cardiac fibrosis by using wild type (WT) and b3 integrin null (b32/ 2) mice for in vivo pressure overload (PO) and in vitro primary cardiac fibroblast phenotypic studies. Compared to WT mice, b32/ 2 mice upon pressure overload hypertrophy for 4 wk by transverse aortic constriction (TAC) showed a substantially reduced accumulation of interstitial fibronectin and collagen. Moreover, pressure overloaded LV from b32/ 2 mice exhibited reduced levels of both fibroblast proliferation and fibroblast-specific protein-1 (FSP1) expression in early time points of PO. To test if the observed impairment of ECM accumulation in b32/ 2 mice was due to compromised cardiac fibroblast function, we analyzed primary cardiac fibroblasts from WT and b32/