Thrombopoietin improved ventricular function and regulated remodeling genes in a rat model of myocardial infarction

• Published in: International journal of cardiology Vol. 167; no. 6; pp. 2546 - 2554
• Main Authors: Chan, Kathy Yuen Yee, Zhou, Ligang, Xiang, Ping, Li, Karen, Ng, Pak Cheung, Wang, Chi Chiu, Li, Ming, Pong, Nga Hin, Tu, Liu, Deng, Haiyan, Kong, Carrie Ka Lai, Sung, Rita Yn Tz
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.09.2013; Elsevier
• Subjects: Animals; Biological and medical sciences; Cardiac remodeling; Cardiology. Vascular system; Cardiovascular; Coronary heart disease; Disease Models, Animal; Endothelial progenitor cells; Heart; Male; Medical sciences; Microarray profiling; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - genetics; Myocardial Infarction - pathology; Myocarditis. Cardiomyopathies; Rats; Rats, Sprague-Dawley; Thrombopoietin; Thrombopoietin - pharmacology; Thrombopoietin - therapeutic use; Ventricular Remodeling - drug effects; Ventricular Remodeling - physiology; Myocardial infarction; Cardiac remodeling; Microarray profiling; Thrombopoietin; Endothelial progenitor cells; Heart; Animal model; Endothelial cell; Rat; Stem cell; Rodentia; Cardiovascular disease; Coronary heart disease; Myocardial disease; Vascular remodeling; Vertebrata; Regulation(control); Mammalia; Gene; Genetics; Circulatory system; Cardiology; Progenitor cell
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2012.06.038

Abstract Background Thrombopoietin (TPO) protects against heart damages by doxorubicin-induced cardiomyopathy in animal models. We aimed to investigate the therapeutic efficacy of TPO for treatment of myocardial infarction (MI) in a rat model and explored the mechanisms in terms of the genome-wide transcriptional profile, TPO downstream protein signals, and bone marrow endothelial progenitor cells (EPCs). Methods Sprague–Dawley rats were divided into 3 groups: Sham-operated, MI (permanent ligation of the left coronary artery) and MI + TPO. Three doses of TPO were administered weekly for 2 weeks, and outcomes were assessed at 4 or 8 weeks post-injury. Results and conclusions TPO treatment significantly improved left ventricular function, hemodynamic parameters, myocardium morphology, neovascularization and infarct size. MI damage upregulated a large cohort of gene expressions in the infarct border zone, including those functioned in cytoskeleton organization, vascular and matrix remodeling, muscle development, cell cycling and ion transport. TPO treatment significantly reversed these modulations. While phosphorylation of janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) was modified in MI animals, TPO treatment regulated phosphorylation of STAT3 and extracellular signal-regulated kinases (ERK), and bone morphogenetic protein 1 (BMP1) protein level. TPO also increased EPC colonies in the bone marrow of MI animals. Our data showed that TPO alleviated damages of heart tissues from MI insults, possibly mediated by multi-factorial mechanisms including suppression of over-reacted ventricular remodeling, regulation of TPO downstream signals and mobilization of endothelial progenitor cells. TPO could be developed for treatment of cardiac damages.