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Phenotypic Characterization of Diabetic Vascular Smooth Muscle Cells
Author(s) -
Husarek Kathryn,
Lucchesi Pamela
Publication year - 2015
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.29.1_supplement.804.6
Subject(s) - endocrinology , medicine , vascular smooth muscle , elastin , myocardin , phenotype , messenger rna , biology , gene expression , smooth muscle , gene , genetics , biochemistry , serum response factor
Objective: We reported a differential pattern of vascular remodeling in type 2 diabetic mice, in which conduit arteries exhibited a characteristic increase in vessel stiffness, but coronary arterioles displayed inward, hypertrophic remodeling and decreased stiffness. This study compared the contribution of vascular smooth muscle cell (VSMC) phenotype and matrix production to the differential remodeling. Methods: Cell lysates were prepared from primary cultures (Passage1) of aortic (ASMC) and coronary arteriole (CASMC) VSMC isolated from control (Db/db) and diabetic (db/db) mice. Basal phenotype markers and matrix secretion were analyzed by qRT‐PCR and immunoblotting. Results: mRNA levels of contractile phenotype markers SM22, calponin1, and α SMA, and protein levels of SM‐MHC and SM22, were significantly decreased in CASMCs vs. ASMCs. Interestingly, mRNA expression of SM22 and calponin1, and protein levels of SM‐MHC were further increased in db/db ASMCs over controls. Collagen1a1 and collagen3a1 mRNA was increased in CASMCs vs. ASMCs. Elastin mRNA increased in db/db ASMCs vs. control ASMCs and decreased in db/db CASMCs vs. control CASMCs. Compared to ASMCs, mRNA levels for the transcriptional regulators myocardin and MRTF‐B were decreased in CASMC, while Klf4 was increased. Conclusions Our results indicate that CASMCs display a less contractile phenotype and altered ECM expression compared to ASMCs, suggesting that VSMC phenotype contributes to vascular bed‐specific remodeling in T2DM. Support to PAL from The Heart Center at Nationwide Children's Hospital.