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INCREASED HEPATOCYTE GROWTH FACTOR IN MONOCROTALINE-INDUCED PULMONARY HYPERTENSION IN RATS

Radik, M.; Kmecova, Z.; Veteskova, J.; Malikova, E.; Krenek, P.; Klimas, J.

Journal of Hypertension: June 2018 - Volume 36 - Issue - p e21
doi: 10.1097/01.hjh.0000539020.52393.11
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Objective: Right-heart catheterization remains the only reliable diagnostic method of right ventricular damage in pulmonary hypertension (PH) and search for a specific biomarker still continues. The aim of this project is to evaluate the significance of plasma levels of hepatocyte growth factor (HGF) and related mRNA expressions in rat model of PH.

Design and method: To induce pulmonary hypertension, 12 weeks old male Wistar rats were subcutaneously injected with monocrotaline (60 mg/kg). They were divided into groups based on experiment duration (1, 2 and 4 weeks) and type of treatment (CON, MCT). Right ventricular pressure was measured in anesthesized rats during catheterisation. Samples of left ventricles (LV), right ventricles (RV), a. pulmonalis, lungs, liver were analysed by RT-qPCR and plasma by ELISA.

Results: MCT-induced PH was characterized by significant progressive increase of right ventricular pressure (2-fold, p < 0,05), breathing frequency (by 40%, p < 0,05) and decrease of oxygen saturation (by 3%, p < 0,05). These were accompanied by increased RV and lungs weights (by 70%, p < 0,05) while weights of other measured organs remained unaffected. In the fourth week after PH induction in MCT group, RV as well as LV mRNA levels of HGF were significantly increased (by 60%, p < 0.05) and significantly reduced in a. pulmonalis, lungs and liver (by 20%, p < 0.05). This was accompanied by an identical pattern of MET receptor expression except for no change in a. pulmonalis and liver. Finally, plasma levels of HGF were significantly elevated (6-fold, p < 0.05) in MCT group when compared to controls after 2 as well as 4 weeks of PH induction.

Conclusions: During the progress of pulmonary hypertension, plasma levels of HGF rise and gene expression of HGF is enhanced selectively in heart ventricles. Consequently, the source of elevated levels of plasma HGF originates from the heart and therefore can present a potential specific biomarker of PH.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovak Republic

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