MOLECULAR BASIS OF CARDIOVASCULAR INJURY

我们希望澄清心血管疾病过程中发生的分子事件 继续我们在强大的心血管系统上的实验工作造成的伤害 毒素、烯丙胺，并将我们实验室的工作扩展到体外细胞 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 并最终确定其假想的尿代谢物，研究 苄胺氧化酶和单胺氧化酶系统的假想作用 通过组织化学、超细胞化学和生化手段，在我们的急性和 AA心血管毒性的慢性大鼠模型。连续形态学 AA损伤的研究将集中在急性内皮和平滑肌 效应，使用H3-胸腺嘧啶核苷评估假想的核激活 AA的有毒代谢物丙烯醛。应用我们的心血管疾病治疗方法 血管内皮细胞，可能还有心肌细胞的毒理学 培养体系中，我们将研究AA的代谢，其毒性 代谢物，我们将尝试评估这些诱导的化生 与体内软骨和骨化生平行的系统 都观察到了。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期 心肌犬模型。继续进行基础形态和毒理学研究 其他脂肪胺和其他对心脏有毒性的化合物将会这样做。

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.