Hepatocyte Growth Factor (HGF) Delivered by Ultrasound-Mediated Destruction of Microbubbles Induces Proliferation of Cardiomyocytes, and Amelioration of Left Ventricular Contractile Function in Doxorubicin-Induced Cardiomyopathy

¹ Kansai Medical University, Osaka, Japan
² Kyoto Institute of Technology, Kyoto, Japan
³ University of Miyazaki, Miyazaki, Japan
⁴ Okayama University, Okayama, Japan

^* To whom correspondence should be addressed. E-mail: ikehara{at}takii.kmu.ac.jp.

	Abstract

It has been reported that myocardial progenitor cells exist even in the post-natal heart, suggesting that myocardial progenitor cells could proliferate under some situations and might improve cardiac function in cardiomyopathy-induced hearts. In this study, recombinant human hepatocyte growth factor (rhHGF) was delivered using ultrasound-mediated destruction of microbubbles (UMDM) into the cardiomyopathy-induced heart by doxorubicin (20mg/kg). Intravenous injection of rhHGF (IV-rhHGF) alone or UMDM alone failed to improve the morphology or the function of the cardiomyopathy-induced heart, but (IV-rhHGF + UMDM) treatment significantly improved the heart morphologically and functionally, and repetitive treatments of (IV-rhHGF + UMDM) enhanced the effects. The number of BrdU⁺ cardiomyocytes significantly increased in the (IV-rhHGF + UMDM)-treated hearts in comparison with the untreated hearts. Moreover, Sca-1⁺ myocardial progenitor cells express c-Met, a receptor for HGF. These results suggest that (IV-rhHGF + UMDM) treatment could morphologically and functionally improve the heart in the case of doxorubicin-induced cardiomyopathy through the proliferation of the myocardial progenitor cells.