Oxidation of arterial extracellular matrix by myeloperoxidase-derived oxidants

众所周知，在动脉粥样硬化的发展过程中，动脉壁中存在的细胞外基质的组成和性质发生变化。在这种基质中发生的变化影响动脉壁的机械和物理性质（例如，其科普由心脏泵送血液产生的高压的能力）和细胞的粘附。已经确定，某些关键细胞类型在改变的或受损的基质上不能很好地粘附或适当地生长，这可能导致关键细胞类型从动脉壁的损失（例如内皮细胞的损失）和-或来自其他来源的细胞的增殖和侵入（例如平滑肌细胞侵入内膜空间）。有间接证据表明，其中一些变化是通过血红素酶髓过氧化物酶形成氧化剂而发生的，该酶是从活化的白色细胞中释放的。在这项研究中，我们将采用最近开发的分析技术来检查的性质的变化，目前在动脉粥样硬化斑块相比，正常的人动脉样本，并调查这种变化出现的机制。我们将寻找证据，或反对，参与髓过氧化物酶衍生的氧化剂在观察到的变化，使用特定的标记，我们已经开发了这种损害的存在。这些信息将允许合理设计干预动脉粥样硬化进展的策略，动脉粥样硬化是澳大利亚人的主要杀手。

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.