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

在发达国家，心血管疾病是人类发病和死亡的主要原因。因此，为了开发新的诊断和治疗策略来治疗相关疾病（如冠状动脉疾病或外周动脉疾病），人们一直致力于确定病变血管的分子和病理生理特征。血管损伤触发血管平滑肌细胞（SMCs）的增殖活性，同时抑制其凋亡能力。SMC扩增和死亡之间的这种暂时不平衡导致细胞数量的大量净增加，导致肌内膜增生。通过抑制内源性抑制剂PDK2激活丙酮酸脱氢酶（PDH），防止SMCs诱导细胞凋亡抵抗，维持稳态生长平衡，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，并筛选用于转化使用的替代候选药物。

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.