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Impaired endothelial cell function in response to oxidative stress: relevance to the pathenogenesis of artherosclerosis - AN0404

Description
This proposal will investigate the mechanisms by which low density lipoprotein (LDL) and oxygen derived free radicals impair normal vascular endothelial cell fuction. We will determine whether endothelial cell dysfunction can be prevented or attenuated by pretreatment with select antioxidants.We have developed an in vitro model of perfused endothelial cell microcarrier cultures in which we can correlate changes solute permeability, nutrient transport a nd agonist-stimulated release of prostacyclin, nitric oxide and endothelin-1. This collaborative proposal involving Kings College London and Reading University provides a basis for evaluting the mechanisms by which oxidant injury and oxidised LDL attenuate endothelium-dependent relaxation in artherosclerotic arteries.
Objective
1. To establish the effects of oxidant stress on endothelial cell junctional solute permeability, impaired endothelial cell release of nitric oxide (NO) and prostacyclin. 2. To determine whether permeability, the arginine-nitric oxide pathway and agonist-induced release of endothelial release of endothelial vasodilators is impaired in atherosclerotic aortae isolated from cholesterol-fed rabbits.
Time-Scale and Cost
From: 1992

To: 1995

Cost: £143,443
Contractor / Funded Organisations
University - London - Kings College
Keywords