Targeting inflammatory processes to treat endothelial dysfunction in cardiovascular diseases

Abstract

Atherosclerosis is a chronic inflammatory disease of the arterial intima characterised by the formation of intimal lesions containing lipids, fibrotic tissue and inflammatory cells. Lesion rupture and thrombosis block blood flow to precipitate a heart attack or stroke. Dysfunction of the arterial endothelium and chronic inflammation are involved at all disease stages. Current interest surrounds identifying the inflammatory mediators involved as this can aid the development of drugs aimed at reducing endothelial dysfunction and vascular inflammation. This thesis tests a novel small molecule drug for its ability to reduce endothelial inflammation and the roles of two inflammatory proteins, heparanase and myeloperoxidase (MPO), as mediators of endothelial dysfunction and atherosclerosis.