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Characterization of vascular smooth muscle cell function in Gravin (AKAP12) truncated mice model in response to angiotensin‐II (866.7)
Author(s) -
Fan Qiying,
Wijaya Cori,
Diaz Diaz Andrea,
McConnell Bradley
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.866.7
Subject(s) - vascular smooth muscle , angiotensin ii , protein kinase c , signal transduction , microbiology and biotechnology , chemistry , matrix metalloproteinase , proliferating cell nuclear antigen , mmp9 , phosphorylation , kinase , medicine , endocrinology , cell growth , downregulation and upregulation , biology , receptor , smooth muscle , biochemistry , gene
Vascular smooth muscle cells (VSMCs), plays a crucial role in the progression of atherosclerosis in response to angiotensin II (Ang II). Gravin, one of the A‐kinase anchoring proteins, targets protein kinase A (PKA), protein kinase C (PKC), and other molecular to different cellular compartments and coordinates signal transduction. The purpose of this study is to investigate the role of gravin in mediating Ang II signaling pathway in VSMCs during atherosclerosis using gravin truncated (gravin‐t/t) mice. Our data showed that Ang II ‐induced migration and proliferation of VSMCs was decreased in gravin‐t/t mice when compared to wild type (WT) mice. Furthermore, gravin‐t/t VSMCs showed no significant difference in PKA activities with or without Ang II treatment, but exhibited a decreased PKC activities and lower intracellular Ca2+ transit after Ang II treatment. These changes were accompanied by significant differences in PKC and PKC‐dependent substrate phosphorylation involving ERK1/2 signaling pathway. In particular, gravin‐t/t mice showed a decreased expression of matrix metalloproteinase 9 (MMP9, a marker of atherosclerosis) and proliferative cell nuclear antigen (PCNA) versus WT mice in the aorta. In conclusion, these findings demonstrate that gravin regulates Ang II ‐induced VSMC proliferation/migration, indicating gravin’s role in the progression of atherosclerosis and/or vascular remodeling.