The major focus of the studies described in this thesis is the interaction of lipoproteins and inflammation in vascular diseases. Early studies describe the role of postprandial lipoproteins in the development of lipid-laden macro phages that are a hallmark of atherosclerotic lesions. These studies paved the way for subsequent studies on the role of lipoprotein modification in atherosclerosis. These included the discovery that LDL present in atherosclerotic lesions had properties that were consistent with oxidative modification. To determine whether this modification was a cause or consequence of the disease, studies were performed using antioxidants. These studies defined the effects of antioxidants on early and mature atherosclerotic lesions, as well as on iatrogenic vascular lesions. My laboratory also studied two potential enzymes that have the potential to generate oxidized lipoprotein; myeloperoxidase and 15-lipoxygenase. The effects of pharmacological inhibition and regulation on the latter enzyme were defined. Studies have also addressed the regulation and function of a major receptor for oxidized LDL, class A scavenger receptor. These include regulation, structure-function, and the effects of cell selective overexpression. These lipoprotein modifications have a well characterized role on the infiltration of macro phages and their subsequent engorgement with lipid. Aberrant lipoprotein metabolism may be a factor underlying the recruitment of T Iymphocytes into lesions. Generally, T Iymphocytes have an under appreciated role in the atherogenic process. Studies using mice deficient in Iymphocyte subclasses and specific cytokines are addressing the issue of this cell type in lesion formation. Finally, we have recently discovered a pronounced inflammatory role of angiotensin II that is associated with the development of atherosclerosis and abdominal aortic aneurysms
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:425851 |
| Date | January 2002 |
| Creators | Daugherty, Alan |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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