Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596835
Title: Effects of macrophages on vascular smooth muscle cell survival in vitro
Author: Boyle, J. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2001
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Abstract:
The synthesis of collagen by vascular smooth muscle cells (VSMCs) is a major determinant of structural stability of human atherosclerotic plaques. Ruptured human atherosclerotic plaques are characterised by a relatively low content of VSMCs, but a high inflammatory cell (macrophage and T lymphocyte) content. Plaques show high levels of VSMC apoptosis. VSMC apoptosis is further increased in ruptured plaques. We hypothesised that inflammatory cells may directly induce VSMC apoptosis. Human peripheral blood mononuclear cells were isolated, monocyte and lymphocyte fractions were prepared, and the ability of inflammatory cells to induce human VSMC apoptosis was examined. Macrophages, but not freshly isolated monocytes or lymphocytes, induced dose-dependent VSMC apoptosis. Macrophages induced apoptosis in human VSMCs from 3 sources coronary media, aortic media and carotid plaque. Apoptosis required direct cell-cell contact or proximity, NO, Fas-L, TNF-R1 and Caspases. NO-donors upregulated VSMC surface Fas and TNF-R1, and enhanced apoptosis induced by Fas-L and TNF-α. Macrophage activation to express surface Fas-L required 5 days maturation in culture, autocrine NO, TNF-R1 and TNF-R2. Immunostaining of ruptured plaques showed that plaque macrophages expressed iNOS, Fas-L and TNF-α and that plaque VSMCs expressed Fas and TNF-R1. In conclusion, macrophages induce VSMC apoptosis in vitro. If this phenomenon truly occurs in vivo, it may promote atherosclerotic plaque rupture.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.596835  DOI: Not available
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