Understanding the involvement of mitochondrial inner membrane hyperpolarization in the development of myointimal hyperplasia

了解线粒体内膜超极化在肌内膜增生发展中的作用

• 批准号: 284075022
• 负责人: Professor Dr. Tobias Deuse
• 金额: --
• 依托单位: Department of Surgery
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/284075022?language=en
• 关键词: Understanding; involvement; mitochondrial; inner; membrane

Cardiovascular disease is the predominant cause of human morbidity and mortality in developed countries. Thus, extraordinary effort has been devoted to determine the molecular and pathophysiological characteristics of the diseased vasculature with the goal of developing novel diagnostic and therapeutic strategies to treat associated diseases (such as coronary artery disease or peripheral artery disease). Vessel injury triggers proliferative activity in vascular smooth muscle cells (SMCs) and concurrently suppresses their ability to undergo apoptosis. This temporary imbalance between SMC amplification and death leads to a largely positive net increase in cellularity, leading to myointimal hyperplasia. Activation of pyruvate dehydrogenase (PDH) via inhibition of its endogenous inhibitor PDK2, prevents the induction of apoptosis resistance in SMCs, maintains the homeostatic growth balance, and prevents vessel narrowing. We now aim to reveal the mechanism of this very effective and novel treatment and to screen for alternative drug candidates for translational use.

心血管疾病是发达国家人类发病和死亡的主要原因。因此，人们付出了巨大的努力来确定患病脉管系统的分子和病​​理生理学特征，目标是开发新的诊断和治疗策略来治疗相关疾病（例如冠状动脉疾病或外周动脉疾病）。血管损伤会触发血管平滑肌细胞（SMC）的增殖活性，同时抑制其凋亡的能力。 SMC 扩增和死亡之间的这种暂时不平衡导致细胞数量大幅净增加，从而导致肌内膜增生。通过抑制其内源性抑制剂 PDK2 激活丙酮酸脱氢酶 (PDH)，防止 SMC 中细胞凋亡抵抗的诱导，维持稳态生长平衡，并防止血管狭窄。我们现在的目标是揭示这种非常有效和新颖的治疗方法的机制，并筛选可供转化使用的替代候选药物。