CHRONIC HYPERGLYCEMIA AND CORONARY HEART DISEASE

我们建议探讨慢性高血糖的机制 减少对心脏的保护。它已经在许多流行病学中得到了证明 研究表明糖尿病会加速男性和女性的动脉粥样硬化。 已经提出了几种机制来解释慢性高血糖症 可能会导致冠心病，但确切的机制是 还有待证实。我们建议用化学方法诱导慢性高血糖 在食蟹猴身上，我们之前已经证明了这是非常好的 动脉粥样硬化和冠心病的模型。我们会 具体评估直接慢性高血糖对心脏功能的影响 糖化和高级糖化最终产物在 动脉壁及其与冠状动脉血管的特殊关系 反应性和动脉粥样硬化。此外，由于未来的 研究的性质、其他因素之间的关系 胰岛素抵抗、脂蛋白浓度和代谢，以及 对血管反应性和动脉粥样硬化的影响可以在这方面进行评估 学习。因此，这项提议的意义在于，它将允许 慢性高血糖对血管紧张素转换酶的影响 冠心病发病机制的一种特征明确的模型 动脉硬化。

We propose to explore the mechanisms by which chronic hyperglycemia reduces cardioprotection. It has been shown in numerous epidemiologic studies that diabetes accelerates atherosclerosis in both men and women. Several mechanisms have been proposed to explain how chronic hyperglycemia can contribute to coronary heart disease, but definitive mechanisms have yet to be proven. We propose to chemically induce chronic hyperglycemia in cynomolgus monkeys which we have previously shown to be excellent models of atherosclerosis and coronary heart disease. We will specifically evaluate the effect of direct chronic hyperglycemia on the accumulation of glycated and advanced glycated end-products in the arterial wall and its specific relationship to coronary vascular reactivity and atherosclerosis. In addition, due to the prospective nature of the study, the relationship between other factors such as insulin resistance and lipoprotein concentrations and metabolism, and the effects on vascular reactivity and atherosclerosis can be assessed in this study. Therefore, the significance of this proposal is that it will allow a direct investigation of the effects of chronic hyperglycemia on mechanisms of coronary heart disease in a well-characterized model of atherosclerosis.