Hypertrophic Versus Apoptotic Response of Vascular Smooth Muscle to β1 Adrenergic Receptor Stimulation




Hannon, Sherry Beth


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Hannon, Sherry Beth., Hypertrophic vs. Apoptotic Response of Vascular Smooth Muscle to β1 Adrenergic Receptor Stimulation. Master of Science (Biotechnology), May, 2004, 64 pp., 3 tables, 16 illustrations, references, 41 titles. This project explores how β1 adrenoceptor (β1-AR) stimulation affects cellular hypertrophy and apoptosis in PAC-1, a cultured rat pulmonary artery cell line. Insights into these responses may further the current understanding of vascular remodeling. Promoter-reporter activity for the hypertrophy-specific gene smooth muscle myosin heavy chain decreased as measured by a luciferase assay when PAC-1 cells were treated with the selective β1-AR agonist dobutamine (DOB) in 0.4% fetal bovine serum (FBS) supplemented media. However, activity of a β1-gal control vector also decreased, and neither response was attenuated by pre-treatment with a β1-AR selective antagonist metoprolol. A MTS [3-(4,5-dimethlythiazol-2-yl)-5-(3-carboxymethoxyphenly)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] viability assay shows that while there is a loss of cells with decreasing amounts of serum, this effect is not exacerbated by DOB in 0.4% FBS. DNA fragmentation assays were inconclusive as to the mode of cell death occurring. However, an increase in Bax/Bcl-2 ratio suggest that apoptosis is induced with DOB treatment in 10% FBS, but that this DOB treatment in 0.4% and serum-free media does not increase this apoptotic index compared to control. Both similar and conflicting cellular responses have been documented in rat neonate cardiomyocytes as well as in murine transgenic models selectively over-expressing adrenergic receptors in the heart. Comparison of the vascular smooth muscle cell response to the cardiomyoctye response may lead to a more tailored use of adrenergic agents for treatment during different stages of cardiovascular disease.