Lipoprotein oxidation, antioxidants and atherosclerosis

我们正在研究主要血管是如何硬化的。这个过程（称为动脉粥样硬化）是心脏病的主要潜在原因，也是澳大利亚人死亡的主要单一原因。我们的研究集中在“氧化理论”，动脉粥样硬化如何发展的最常见的理论之一。因此，携带脂肪的颗粒（称为脂蛋白）中的脂肪穿透血管壁，在那里它们由于腐臭而引起疾病。这是公众对抗氧化剂补充剂对抗心脏病感兴趣的主要原因。然而，目前还不清楚腐臭脂肪是动脉粥样硬化的原因还是结果，我们最近发现，这两个过程可以在疾病的动物模型中分离。本申请使用几种不同的动脉粥样硬化动物模型，解决了脂肪酸败的过程是否通常与动脉粥样硬化无关的问题。我们将区分不同的化学途径，产生不同类型的腐臭脂肪，腐臭脂肪和“腐臭”蛋白质之间。迄今尚未进行这类研究。我们的基本假设是，脂蛋白脂肪变臭的过程是一个结果，而不是动脉粥样硬化和心脏病的原因。通过测试这一假设，我们将提供一个理论基础，以防止酸败脂肪积累的抗氧化剂补充剂是否可能有利于预防心脏病。这直接关系到公众健康。我们的研究还解决了抗氧化剂（如果不是通过防止脂肪酸败）如何减轻动脉粥样硬化的问题。我们将重点关注一种特殊的合成抗氧化剂，有强有力的证据表明，它有利于防止接受冠状动脉成形术的人血管再狭窄。这些研究有可能为开发治疗心脏病的新药提供新的线索。

We are studying how major blood vessels harden. This process (called atherosclerosis) is the major underlying cause of heart disease, the major single cause of death of Australians. Our research focusses on the 'Oxidation Theory', one of the most common theories of how atherosclerosis develops. Accordingly, fats in fat-carrying particles (called lipoproteins) penetrate the walls of blood vessels, where they cause disease as a result of going rancid. This is a primary reason for the general public's interest in antioxidant supplements to combat heart disease. However, it is not clear at present whether rancid fats is a cause or consequence of atherosclerosis, and we recently showed that the two processes can be dissociated in an animal model of the disease. This application addresses the question of whether the process of fats going rancid can be generally dissociated from atherosclerosis, using several different animal models of the disease. We will distinguish different chemical pathways that give rise to different types of rancid fats, and between rancid fats and 'rancid' proteins. Such studies have not been carried out to date. Our underlying hypothesis is that the process of lipoprotein fat going rancid is a consequnece rather than a cause of atherosclerosis and heart disease. By testing this hypothesis, we will provide a rationale for whether antioxidant supplements aimed at preventing rancid fats from accumulating are likely of benefit in terms of preventing heart disease. This is of direct interest to public health. Our studies also address the issue of how antioxidants (if not through preventing fats from going rancid) attenuate atherosclerosis. We will focus on a particular synthetic antioxidant for which there is strong evidence that it is beneficial in preventing the re-narrowing of blood vessels in humans undergoing coronary angioplasty. These studies have the potential to provide new clues for the development of novel drugs against heart disease.