Oxidation of arterial extracellular matrix by myeloperoxidase-derived oxidants

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/119240

Funding Status
Closed

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Funded Activity Summary

It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on altered or damaged matrix and this can result in either the loss of key cell types from the artery wall (e.g. loss of endothelial cells) and - or the proliferation and invasion of cells from other sources (e.g. smooth muscle cell invasion into the intimal space). There is circumstantial evidence that some of these changes occur via the formation of oxidants by the heme enzyme myeloperoxidase which is released from activated white cells. In this study we will employ recently developed analytical techniques to examine the nature of the alterations that are present in atherosclerotic plaques in comparison to normal human artery samples, and investigate the mechanisms by which such alterations arise. We will seek evidence for, or against, the involvement of myeloperoxidase-derived oxidants in the observed changes using specific markers which we have developed for the presence of such damage. This information will allow the rational design of strategies to interfere with the progression of atherosclerosis, which is the major killer of Australians.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $183,266.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Analytical Biochemistry

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Atherosclerosis | Extracellular Matrix | Extracellular matrix degradation | Free radicals | Hypochlorite | Myeloperoxidase | Protein oxidation | Vascular disease

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