支架内再狭窄(血管或心脏瓣膜变窄的现象)是用心脏支架(金属或塑料管子)来治疗冠状动脉病所经常发生的一种并发症。这种状况以平滑肌细胞增生以及肌内膜或最内部血管壁的细胞增生为特征。Sonja Schrepfer及同事对这些增生细胞在形成过程中的代谢特点进行了表征，发现存在瞬态线粒体重新编程和代谢被改变。他们发现，药物“二氯乙酸盐”(已知能够抑制肿瘤生长) 在若干临床前模型中能够防止这些代谢改变中的一些，减少肌内膜增生——至少部分是通过抑制“丙酮酸脱氢酶激酶-2”来发挥这种作用的。
Despite the introduction of antiproliferative drug-eluting stents, coronary heart disease remains the leading cause of death in the United States1. In-stent restenosis and bypass graft failure are characterized by excessive smooth muscle cell (SMC) proliferation2, 3 and concomitant myointima formation with luminal obliteration. Here we show that during the development of myointimal hyperplasia in human arteries, SMCs show hyperpolarization of their mitochondrial membrane potential (ΔΨm) and acquire a temporary state with a high proliferative rate and resistance to apoptosis. Pyruvate dehydrogenase kinase isoform 2 (PDK2) was identified as a key regulatory protein, and its activation proved necessary for relevant myointima formation. Pharmacologic PDK2 blockade with dichloroacetate or lentiviral PDK2 knockdown prevented ΔΨm hyperpolarization, facilitated apoptosis and reduced myointima formation in injured human mammary and coronary arteries, rat aortas, rabbit iliac arteries and swine (pig) coronary arteries. In contrast to several commonly used antiproliferative drugs, dichloroacetate did not prevent vessel re-endothelialization. Targeting myointimal ΔΨm and alleviating apoptosis resistance is a novel strategy for the prevention of proliferative vascular diseases.