Clinical Pharmacology research regarding cardiovascular biomarkers and experimental system for the assessment of drugs in humans

我们需要更具体的、相关的和可预测的生物标志物，不仅用于日常实践，而且用于开发预防心血管事件的新药。我们的研究项目首次揭示了糖尿病和IGT患者不仅内皮功能受损，平滑肌对NO的反应也受损。这些血管功能受损与胰岛素敏感性显著相关。我们还发现，FFA的升高显著损害了内皮功能、心肌微循环流变功能、胰岛素敏感性、白细胞功能和血管紧张素II形成活性的增强。RAS抑制剂和二氢吡啶钙拮抗剂显著但不能完全阻止FFA的这些作用。阐明了FFA诱导内皮功能和胰岛素抵抗的机制，建立了抗动脉粥样硬化药物的人体评价实验体系。

We need more specific, relevant and predictive biomarkers for not only daily practice but also development of new drugs for the prevention of cardiovascular events. Our research project firstly revealed that not only endothelial function but also smooth muscle responses to NO were impaired in not only diabetic but also IGT patients. These impaired vascular functions were significantly associated with insulin sensitivity. We also showed that elevation of FFA significantly impaired endothelial function, rheological function of myocardial microcirculation, insulin sensitivity and enhanced leukocyte function and angiotensin II forming activity. RAS inhibitors as well as dihydropyridine calcium antagonists significantly but not completely prevented these effects of FFA. We clarified mechanisms for FFA induced endothelial function and insulin resistance and established experimental system for the assessment antiatherosclerotic drugs in human.