Myeloperoxidase-catalysed damage to arterial extracellular matrix and its consequences

一种血红素酶(髓过氧化物酶)已被证明存在于病变的人类动脉中，据报道，这种酶通过催化高活性氧化剂的形成而促进动脉疾病的发展。最近的研究表明，这种酶的水平与冠状动脉疾病的存在密切相关，这种酶可能在斑块破裂中发挥作用，斑块破裂是导致冠状动脉猝死的主要原因。也有报道称，在晚期的人类动脉粥样硬化病变中，金属离子水平升高。在最近的实验中，我们已经证明了髓过氧化物酶产生的产物可以与金属离子和超氧阴离子相互作用，并且这个过程导致了损害的加剧。髓过氧化物酶产生的氧化剂与金属离子之间的这种协同作用可能至少在一定程度上解释了在人体病变中检测到的复杂产物混合物，并导致病变结构减弱，并有助于增加斑块破裂的可能性。这项研究将研究正常动脉和培养细胞对细胞外基质物质的潜在影响和机制，我们将研究在什么情况下发生相互作用，以及这些反应是否可能在斑块破裂中发挥关键作用。我们还将研究细胞外基质损伤所产生的物质如何影响生长在这种支架上的细胞，以及这是否可能是发展中的动脉粥样硬化病变内细胞行为改变的部分原因。详细了解哪些过程在斑块破裂中是重要的，这是开发新的治疗策略的必要前提。

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.