MOLECULAR BASIS OF CARDIOVASCULAR INJURY

我们希望阐明心血管疾病发生的分子事件， 通过继续我们对有效的心血管损伤的实验工作， 毒素，烯丙胺，并扩大我们的实验室的工作，在体外细胞 培养系统，心肌缺血的研究，以及其他 心血管毒素 为了进一步研究烯丙胺（AA），我们将分离 并明确确定其假设的尿液代谢物，研究 苄胺氧化酶和单胺氧化酶系统的假设作用 通过组织化学，超细胞化学和生物化学手段，在我们的急性和 AA心血管毒性慢性大鼠模型。 连续形态学 AA病变的研究将集中在急性内皮和平滑肌 影响，使用H3-胸苷评估假设的核活化， AA的有毒代谢物丙烯醛 应用我们的心血管治疗方法 对内皮平滑肌和可能的心肌细胞的毒理学 培养系统，我们将研究AA的代谢，其毒性， 代谢物，我们将试图评估这些诱导化生 系统平行于体内软骨和骨化生， 已经观察到。 还原型和氧化型谷胱甘肽和谷胱甘肽 过氧化物酶，转移酶和还原酶将在缺血性 犬心肌模型。 继续进行基本形态学和毒理学研究 其他脂肪胺和其他心脏毒性化合物。

We hope to clarify the molecular events occurring during cardiovascular injury by continuing our experimental work on the potent cardiovascular toxin, allylamine, and expanding our laboratory's work to in vitro cell culture systems, the investigation of myocardial ischemia, and other cardiovascular toxins. To further study allylamine (AA), we will isolate and definitively identify its hypothesized urinary metabolites, study the hypothetical role of Benzylamine oxidase and the monoamine oxidase systems by histochemical, ultracytochemical, and biochemical means in our acute and chronic rat models of AA cardiovascular toxicity. Continued morphologic studies of AA lesions will focus on acute endothelial and smooth muscle effects, using H3-Thymidine to assess hypothetical nuclear activation by AA's toxic metabolite, acrolein. Applying our methods of cardiovascular toxicology to endothelial smooth muscle, and possibly myocardial cell culture systems, we will investigate the metabolism of AA, toxicity of its metabolites, and we will attempt to assess metaplasia induced in these systems in parallel to the in vivo cartilagenous and bony metaplasia we have observed. Glutathione - both reduced and oxidized - and glutathione peroxidase, transferase and reductase will be studied in an ischemic myocardial dog model. Continued basic morphologic and toxicologic studies of other aliphatic amines, and other cardiotoxic compounds will be done.