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09 March 2016 : Original article  

Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery

Shaojun LiABCDEF, Dong HanABCD, Yonghong ZhangABC, Xinming XieABC, Rui KeABC, Yanting ZhuABC, Lu LiuABC, Yang SongABC, Lan YangABC, Manxiang LiABCDEFG

DOI: 10.12659/MSMBR.897505

Med Sci Monit Basic Res 2016; 22:27-33


BACKGROUND: The current study was performed to investigate the effect of adenosine monophosphate (AMP) – activated protein kinase (AMPK) activation on the extracellular matrix (ECM) remodeling of pulmonary arteries in pulmonary arterial hypertension (PAH) and to address its potential mechanisms.

MATERIAL AND METHODS: PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) into Sprague-Dawley rats. Metformin (MET) was administered to activate AMPK. Immunoblotting was used to determine the phosphorylation and expression of AMPK and expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Gelatin zymography was performed to determine the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9.

RESULTS: Activation of AMPK by MET significantly reduced the right ventricle systolic pressure and the right ventricular hypertrophy in MCT-induced rat PAH model, and partially inhibited the ECM remodeling of pulmonary arteries. These effects were coupled with the decrease of MMP-2/9 activity and TIMP-1 expression.

CONCLUSIONS: This study suggests that activation of AMPK benefits PAH by inhibiting ECM remodeling of pulmonary arteries. Enhancing AMPK activity might have potential value in clinical treatment of PAH.

Keywords: AMP-Activated Protein Kinases - metabolism, Enzyme Activation - drug effects, Extracellular Matrix - pathology, Hypertension, Pulmonary - pathology, Matrix Metalloproteinase 2 - metabolism, Metformin - pharmacology, Monocrotaline - pharmacology, Pulmonary Artery - enzymology, Random Allocation, Tissue Inhibitor of Metalloproteinase-1 - metabolism, Vascular Remodeling - drug effects

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416