HGF/Met Axis in Heart Function and Cardioprotection

Abstract

Hepatocyte growth factor (HGF) and its tyrosine kinase receptor (Met) play important roles in myocardial function both in physiological and pathological situations. In the developing heart, HGF influences cardiomyocyte proliferation and differentiation. In the adult, HGF/Met signaling controls heart homeostasis and prevents oxidative stress in normal cardiomyocytes. Thus, the possible cardiotoxicity of current Met-targeted anti-cancer therapies has to be taken in consideration. In the injured heart, HGF plays important roles in cardioprotection by promoting: (1) prosurvival (anti-apoptotic and anti-autophagic) effects in cardiomyocytes, (2) angiogenesis, (3) inhibition of fibrosis, (4) anti-inflammatory and immunomodulatory signals, and (5) regeneration through activation of cardiac stem cells. Furthermore, we discuss the putative role of elevated HGF as prognostic marker of severity in patients with cardiac diseases. Finally, we examine the potential of HGF-based molecules as new therapeutic tools for the treatment of cardiac diseases.

Electrical Stimulation of pediatric cardiac-derived c-kit+ progenitor cells improves retention and cardiac function in right ventricular heart failure

“…We found increased levels of FGF release from ES-CPCs compared with control cells, which may activate endogenous stem cell growth after cell injection and contribute to the increased functional effect of ES-CPCs. We also observed increased HGF release, which has been implicated in cardiac regeneration and CPC activation [55], decreased MMP-9 release, which has a negative effect on heart contractility [41], and increased angiogenin release, which has been shown to increase angiogenesis and improve LV function in myocardial infarction rat models [37,56,57]. The release of pro-angiogenic factors and localization to the epicardial layer in vivo suggest that ES may induce CPCs to differentiate toward an endothelial phenotype.…”

Molecular Engineering Strategies Tailoring the Apoptotic Response to a MET Therapeutic Antibody

“…It is well known that wild type MET signaling has a protective role in lung fibrosis [32], liver cirrhosis [33], acute pancreatitis [34], and acute kidney injury [35]. Moreover, MET activation protects cardiomyocytes from apoptosis through inhibition of the mitochondrial pathway [12,36,37]. All these evidences suggest the use of MET agonists, such as short-sc25, in association with chemotherapy for the treatment of tumors that are not dependent on MET activation.…”

HGF Treatment Promotes Cardiac Function and Cardiac Repair: Meta-analysis of Pig Models With Myocardial Infarction

“…HGF, a promising biomarker for CHD, is released into the bloodstream following the damage of endothelial cells [24]. In addition, HGF has been shown to attenuate chronic tissue damage, promote angiogenesis, inhibit brosis and apoptosis, regulate in ammation and improve prognosis [25,26] in various ischemic disease models such as MI [27] and peripheral arterial occlusive disease (PAOD) [28]. The biological function of HGF is mediated by its unique tyrosine kinase receptor c-Met [29], and the activation of c-Met receptor further activates many intracellular signaling pathways including RASmitogen activated protein kinase (MAPK), signal transducer and activator of transcription (STAT), phosphatidylinositol-3 kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) and β-catenin pathway [30][31][32].…”