Angiotensin II-induced Apoptosis in Vascular Smooth Muscle Cells: Differential Effects in Human Saphenous Vein and Human Internal Mammary Artery
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Authors
Gritzuk, Michael Mark
Issue Date
2006-08
Volume
Issue
Type
Thesis
Language
en_US
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Alternative Title
Abstract
Coronary artery bypass grafting serves as a viable treatment for arterial vascular occlusions. However, the likelihood for developing restenosis following coronary artery bypass grafting surgery remains a major threat. Subsequently, assessing the physiological differences of conduit bypass vessels has become a crucial topic for vascular research. The exact mechanisms underlying restenosis development are unknown, but many mediators, including angiotensin II, have been implicated.
The hypothesized will be examined that angiotensin II induces differential responses in the vascular smooth muscle cells (VSMCs) of human saphenous vein (SV) and human internal mammary artery (IMA). To test this hypothesis, VSMCs were isolated from surgical specimens of SV and IMA obtained from patients who had undergone coronary artery bypass graft surgery. SV and IMA VSMCs were serum starved for synchronization and treated with various concentrations of angiotensin II. Apoptosis was measured using annexin V-FITC and propidium iodide followed by flow cytometric analysis. Protein expression of Bax, Bcl-2, and phospho-p38 MAP kinase was examined by Western Blot.
The data revealed three major findings: (1) Angiotensin II induced significant apoptosis in VSMCs of the SV following 8 hours of treatment, whereas there was no pro- apoptotic effect of angiotensin II on VSMCs of the IMA. The effect of angiotensin II to induce apoptosis in SV VSMCs was supported by the up regulation of a pro-apoptotic protein, Bax, and decrease in the expression of a pro-survival protein, Bcl-2. Angiotensin II had no effect on Bax protein expression in IMA VSMC, but increased Bcl-2 protein expression.
Angiotensin II induced the phosphorylation of p38 MAP kinase in SV VSMCs, whereas this effect was not observed in IMA VSMC, and (3) inhibition of p38 MAP kinase using SB 203580 decreased angiotensin II-induced apoptosis in SV VSMCs, thereby suggesting a linkage between p38 MAP kinase and angiotensin II-induced apoptosis. The current research demonstrated a differential response to angiotensin II- induced apoptosis between VSMCs of SV in comparison to IMA. The clinical significance of these findings warrants further investigations.
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Publisher
Creighton University
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Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.
Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.
Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.