Shikonin improves pulmonary vascular remodeling in monocrotaline‑induced pulmonary arterial hypertension via regulation of PKM2

Li,Wenfeng; Chen,Wenjuan; Peng,Hongyan; Xiao,Zhenghui; Liu,Jinqiao; Zeng,Yunhong; Huang,Ting; Song,Qingqing; Wang,Xun; Xiao,Yunbin

doi:10.3892/mmr.2023.12947

Shikonin improves pulmonary vascular remodeling in monocrotaline‑induced pulmonary arterial hypertension via regulation of PKM2

Authors:
- Wenfeng Li
- Wenjuan Chen
- Hongyan Peng
- Zhenghui Xiao
- Jinqiao Liu
- Yunhong Zeng
- Ting Huang
- Qingqing Song
- Xun Wang
- Yunbin Xiao
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Affiliations: Department of Ultrasound, Hunan Children's Hospital, Changsha, Hunan 410007, P.R. China, Hunan Children's Research Institute, Hunan Children's Hospital, Changsha, Hunan 410007, P.R. China, Intensive Care Unit, Hunan Children's Hospital, Changsha, Hunan 410007, P.R. China, Department of Cardiology, Hunan Children's Hospital, Changsha, Hunan 410007, P.R. China
Published online on: February 1, 2023 https://doi.org/10.3892/mmr.2023.12947
Article Number: 60
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pulmonary arterial hypertension (PAH), a fatal disease with an insidious onset and rapid progression, shows characteristics such as increases in pulmonary circulatory resistance and pulmonary arterial pressure, and progressive right heart failure. Shikonin can reduce right ventricular systolic pressure in chronically hypoxic mice. However, the mechanisms underlying the protective effect of shikonin against PAH pathogenesis have only been sporadically identified. The present study evaluated whether inhibiting the expression of pyruvate kinase M2 (PKM2) contributed to the improvement of pulmonary vascular remodeling in PAH rats induced by monocrotaline (MCT) treatment. Hemodynamic parameters were assessed using echocardiography and right ventricular catheterization. Right ventricular hypertrophy index analysis and hematoxylin and eosin staining were used to evaluate the degree of pulmonary vascular and right heart remodeling. Moreover, PKM2, p‑PKM2, ERK, p‑ERK, glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA) protein expression levels were semi‑quantified using western blotting. The expression and distribution of PKM2 were assessed using immunofluorescence microscopy. The present study demonstrated that MCT treatment caused pulmonary arterial hypertension and pulmonary vascular remodeling in experimental rats. Shikonin improved hemodynamics and pulmonary vascular remodeling in MCT‑induced PAH rats, decreased aerobic glycolysis and downregulated PKM2, p‑PKM2, p‑ERK, GLUT 1 and LDHA protein expression levels. Shikonin improved experimental pulmonary arterial hypertension hemodynamics and pulmonary vascular remodeling at least partly through the inhibition of PKM2 and the resultant suppression of aerobic glycolysis. These results provide a novel understanding of possible new treatment targets for PAH.

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