Project 5 - Metabolomic Analysis of Atherothrombosis

心血管疾病(CVD)是糖尿病患者死亡的主要原因，急性 患有2型糖尿病的年轻人的冠状动脉综合征(ACS)和总死亡率是不患有2型糖尿病的年轻人的几倍 糖尿病(T2D)。然而，T2D导致更大的心血管疾病风险的机制尚不清楚。 而且还没有开发出针对糖尿病的心血管疾病治疗方案。冠状动脉内发生急性冠脉综合征 血栓会阻碍冠脉血流，导致心肌缺血，并导致大部分 T2D不可逆性心肌损害。尽管在诊断急性冠脉综合征方面取得了很大的进展，但所有的 目前的急性冠脉综合征生物标志物衡量的是结果，即心肌坏死，而不是病因和治疗 靶-动脉粥样硬化血栓形成。在事件开始之前，识别动脉粥样硬化血栓形成心肌梗死的能力 不可逆转的心肌坏死，并快速鉴别动脉粥样硬化性血栓形成与非动脉粥样硬化性急性冠脉综合征 将大大提高T2D患者治疗急性冠脉综合征的安全性和有效性。长期目标 本项目的主要目的是开发一种区分动脉粥样硬化性血栓形成患者和非动脉粥样硬化性血栓形成患者的生物标记物。 在患有T2D的患者中。这种方法不仅将提高诊断的准确性，而且还有可能 识别冠状动脉血栓形成开始时的事件，在“不可避免的”心肌坏死之前，允许发生更多 及时、有针对性的干预措施。因此，使用有针对性和无偏见的代谢学方法，我们 计划确定动脉粥样硬化血栓形成的特定生物标志物。我们的中心假设是动脉粥样硬化血栓形成事件 与罪魁祸首病变中氧化脂质代谢产物的产生增加有关，或者 由动脉粥样硬化血栓形成事件本身产生，对这些代谢物的测量将允许早期 而动脉粥样硬化性血栓形成的准确诊断是T2D患者。

Cardiovascular disease (CVD) is the leading cause of death in individuals with diabetes with rates of acute coronary syndrome (ACS) and total mortality several fold higher in younger adults with versus without type 2 diabetes (T2D). Nevertheless, the mechanisms that impart greater CVD risk in T2D are not well understood and no diabetes-specific CVD treatment regimens have been developed. ACS occurs when intracoronary thrombus obstructs coronary flow to produce myocardial ischemia and is responsible for the majority of irreversible myocardial damage in T2D. Although great advances have been made in diagnosing ACS, all of the current ACS biomarkers measure the result, myocardial necrosis, and not the cause and therapeufic target -atherothrombosis. The ability to identify atherothrombotic-MI at the start of the event, prior to irreversible myocardial necrosis, and quickly disfinguish atherothrombotic from non-atherothrombofic ACS would materially increase the safety and effectiveness of ACS treatment in T2D patients. The long-term goal of this project is to develop a biomarker which differentiates atherothrombotic from non-atherothrombotic Ml in patients with T2D. Such an approach will not only improve diagnostic accuracy but could also potentially identify events at the start of coronary thrombosis, prior to "inevitable" myocardial necrosis, allowing for more prompt and targeted interventions. Hence, using both targeted and unbiased metabolomic approaches, we plan to identify specific biomarkers of atherothrombosis. Our central hypothesis is atherothrombotic events are associated with increased production of metabolites derived from oxidized lipids in the culprit lesion or generated by the atherothrombotic event itself and that measurement of these metabolites will allow for eariy and accurate diagnosis of atherothrombotic Ml is T2D patients.