Up-regulation of hexokinase1 in the right ventricle of monocrotaline induced pulmonary hypertension

Respiratory Research

Zhi-cheng Jing²  Yang Zheng³  Kai Sun²  Xiao-jian Wang²  Mei-hong Qiu¹  Wei-hua Zhang³ 

[1] Department of Cardiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China;Thrombosis and vascular Medicine Center, College & Chinese Academy of Medical Sciences, State Key Lab of Cardiovascular disease, National Center for Cardiovascular disease, Fu Wai Hospital, Peking Union Medical, 167 Beilishi Road, Beijing 100037, China;The Center of Cardiovascular Disease, The First Hospital of Jilin University, Changchun, China

关键词: Hexokinase 1;    Glycolysis;    Right heart failure;    Pulmonary hypertension;   

Others  :  1137257
DOI  :  10.1186/s12931-014-0119-9

 received in 2014-07-23, accepted in 2014-09-30,  发布年份 2014

【 摘 要 】

Background

Pulmonary arterial hypertension (PAH) is a proliferative arteriopathy associated with a glycolytic shift during heart metabolism. An increase in glycolytic metabolism can be detected in the right ventricle during PAH. Expression levels of glycolysis genes in the right ventricle during glycolysis that occur in monocrotaline (MCT)-induced pulmonary hypertension (PH) remain unknown.

Methods

PH was induced by a single subcutaneous injection of MCT (50 mg/kg) into rats, eventually causing right heart failure. Concurrently, a control group was injected with normal saline. The MCT-PH rats were randomly divided into three groups according to MCT treatment: MCT-2 week, 3 week, and 4 week groups (MCT-2w, 3w, 4w). At the end of the study, hemodynamics and right ventricular hypertrophy were compared among experimental groups. Expression of key glycolytic candidate genes was screened in the right ventricle.

Results

We observed an increase in mean pulmonary arterial pressure, right ventricular systolic pressure and right ventricular hypertrophy index three weeks following MCT injection. Alterations in the morphology and structure of right ventricular myocardial cells, as well as the pulmonary vasculature were observed. Expression of hexokinase 1 (HK1) mRNA began to increase in the right ventricle of the MCT-3w group and MCT-4w group, while the expression of lactate dehydrogenase A (LDHA) was elevated in the right ventricle of the MCT-4w group. Hexokinase 2(HK2), pyruvate dehydrogenase complex α1 (PDHα1), and LDHA mRNA expression showed no changes in the right ventricle. HK1 mRNA expression was further confirmed by HK1 protein expression and immunohistochemical analyses. All findings underlie the glycolytic phenotype in the right ventricle.

Conclusions

There was an increase in the protein and mRNA expression of hexokinase-1 (HK1) three and four weeks after the injection of monocrotaline in the right ventricle, intervention of HK1 may be amenable to therapeutic intervention.

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

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