Eukaryotic elongation factor 2 kinase mediates monocrotaline-induced pulmonary arterial hypertension via reactive oxygen species-dependent vascular remodeling

American Journal of Physiology. Heart and Circulatory Physiology
Satoshi KameshimaHideyuki Yamawaki

Abstract

Pulmonary arterial (PA) hypertension (PAH) is a progressive and lethal disease that is caused by increased vascular contractile reactivity and structural remodeling. These changes contribute to increasing pulmonary peripheral vascular resistance, finally leading to right heart failure and death. Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca(2+)/calmodulin-dependent protein kinase. We previously revealed that eEF2K protein increases in the mesenteric artery from spontaneously hypertensive rats and partly mediates the development of hypertension via a promotion of ROS-dependent vascular inflammatory responses and proliferation and migration of vascular smooth muscle cells. However, a role of eEF2K in the pathogenesis of PAH is unknown. In the present study, we tested the hypothesis that eEF2K may be involved in the pathogenesis of PAH. PAH was induced by a single intraperitoneal injection of monocrotaline (MCT; 60 mg/kg) to rats. A specific eEF2K inhibitor, A-484954 (2.5 mg·kg(-1)·day(-1)), was intraperitoneally injected for 14 days. Long-term A-484954 treatment inhibited MCT-induced increased PA pressure. It was revealed that A-484954 inhibited MCT-induced PA hypertrophy and fibrosis but not impairment of endothelium-dep...Continue Reading

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Citations

Dec 25, 2015·Biochemical and Biophysical Research Communications·Satoshi KameshimaHideyuki Yamawaki
Mar 30, 2016·Pflügers Archiv : European journal of physiology·Keisuke ImotoHideyuki Yamawaki
May 20, 2017·The American Journal of Chinese Medicine·Lin-Bo YuanQing-Hua Hu
Nov 16, 2018·The Journal of Veterinary Medical Science·Tomoko KodamaHideyuki Yamawaki
Feb 21, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Rui XiaoQinghua Hu
Jul 10, 2019·International Journal of Cancer. Journal International Du Cancer·Ying ZhouKaikai Shen
Aug 5, 2017·Pflügers Archiv : European journal of physiology·Yuzaburo SakamotoHideyuki Yamawaki
Jan 27, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Wei FengManxiang Li
May 10, 2017·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Satoshi KameshimaHideyuki Yamawaki
Sep 24, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Rubin TanQinghua Hu

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