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

心血管疾病是发达国家人类发病率和死亡率的主要原因。因此，特别的努力已经致力于确定患病脉管系统的分子和病理生理学特征，目的是开发新的诊断和治疗策略以治疗相关疾病（例如冠状动脉疾病或外周动脉疾病）。血管损伤触发血管平滑肌细胞（SMC）的增殖活性，同时抑制其进行凋亡的能力。SMC扩增和死亡之间的这种暂时性失衡导致细胞构成的大量正性净增加，从而导致肌内膜增生。丙酮酸脱氢酶（PDH）通过抑制其内源性抑制剂PDK2而被激活，从而防止SMC中凋亡抗性的诱导，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机制，并筛选用于翻译的替代候选药物。

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.