巴基斯坦卢比
心室
肺动脉高压
PARP1
医学
内科学
心脏病学
糖酵解
生物
丙酮酸激酶
基因
聚合酶
聚ADP核糖聚合酶
遗传学
新陈代谢
作者
Takashi Shimauchi,Olivier Boucherat,Tetsuro Yokokawa,Yann Grobs,Wenhui Wu,Mark Orcholski,Sandra Martineau,Junichi Omura,Ève Tremblay,Kana Shimauchi,Valérie Nadeau,Sandra Breuils‐Bonnet,Roxane Paulin,François Potus,Steeve Provencher,Sébastien Bonnet
标识
DOI:10.1016/j.jacbts.2022.01.005
摘要
The authors show that increased poly(adenosine diphosphate–ribose) polymerase 1 (PARP1) and pyruvate kinase muscle isozyme 2 (PKM2) expression is a common feature of a decompensated right ventricle in patients with pulmonary arterial hypertension and animal models. The authors find in vitro that overactivated PARP1 promotes cardiomyocyte dysfunction by favoring PKM2 expression and nuclear function, glycolytic gene expression, activation of nuclear factor κB–dependent proinflammatory factors. Pharmacologic and genetic inhibition of PARP1 or enforced tetramerization of PKM2 attenuates maladaptive remodeling improving right ventricular (RV) function in multiple rodent models. Taken together, these data implicate the PARP1/PKM2 axis as a critical driver of maladaptive RV remodeling and a new promising target to directly sustain RV function in patients with pulmonary arterial hypertension.
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