Myeloperoxidase-catalysed damage to arterial extracellular matrix and its consequences [ 2004 - 2006 ]

Research Grant

Researchers: Prof Michael Davies (Principal investigator)

Brief description A heme enzyme (myeloperoxidase) has been shown to be present in the lesions present in diseased human arteries, and it has been reported that this enzyme contributes to the development of arterial disease via its ability to catalyse the formation of highly reactive oxidants. Recent studies have shown that the level of this enzyme correlate strongly with the presence of coronary artery disease, and that this enzyme may play a role in plaque rupture, a leading cause of sudden coronary death. It has also been reported that elevated levels of metal ions are present in advanced human atherosclerotic lesions. In recent experiments we have shown that products generated by myeloperoxidase can interact with metal ions and superoxide radicals, and that this process results in an exacerbation of damage. This synergism between the oxidants generated by myeloperoxidase and metal ions may explain, at least in part, the complex mixture of products detected in human lesions and be responsible for the weakening of lesion structure and contribute to an enhanced likelihood of plaque rupture. This study will examine the potential effects and mechanisms of damage to extracellular matrix materials from normal arteries and cultured cells We will examine under what circumstances interactions occur and whether these reactions may play a key role in plaque rupture. We will also examine how materials arising from damage to the extracellular matrix may affect the cells whic grow upon this scaffolding, and whether this may be partly responsible for altered behaviour of cells within dveloping atherosclerotic lesions. A detailed knowledge of which processes are important in plaque rupture is an essential pre-requisite to the development of new therapeutic strategies.

Funding Amount $AUD 384,750.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant