QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jin, H. Articles by Paoni, N. F. Search for Related Content PubMed PubMed Citation Articles by Jin, H. Articles by Paoni, N. F.

CARDIOVASCULAR

Early Treatment with Hepatocyte Growth Factor Improves Cardiac Function in Experimental Heart Failure Induced by Myocardial Infarction

Departments of Cardiovascular Research (H.J., R.Y., W.L., R.K.O., N.F.P.), Molecular Oncology (R.S., Z.Z.), Pathology (D.A.E.), and Recovery Science (D.K.), Genentech, Inc., South San Francisco, California

Plasma levels of hepatocyte growth factor (HGF) are increased within hours of cardiac ischemia/reperfusion in rats, and HGF has been shown to be cardioprotective toward acute ischemic injury. Myocardial levels of HGF mRNA and protein are increased for several days after myocardial infarction (MI), however, indicating a possible additional protective effect of HGF toward the progression of MI to heart failure. The purpose of this study was to determine whether HGF administration during the time course of endogenous cardiac HGF induction would lead to long-term improvement in cardiac function in rats with MI. MI was induced by 2-h occlusion of the left coronary artery, followed by reperfusion. HGF was given by intravenous infusion at 0.45 mg/kg/day for 6 days beginning on the day after surgery. Cardiac function and hemodynamic parameters were measured by using indwelling catheters and perivascular flow probes in conscious animals 8 weeks post-MI. Myocardial infarcts were approximately 30% of the left ventricle, and there was no difference in infarct size between the vehicle-treated and HGF-treated groups. Compared with untreated sham-operated rats, vehicle-treated MI animals had significantly lower cardiac index and stroke volume index and higher systemic vascular resistance, indicating heart failure developed. Treatment with HGF caused a significant increase in cardiac index and stroke volume index and a reduction in systemic vascular resistance in rats with MI, restoring these parameters close to those observed in sham-operated control animals. These results provide direct evidence that HGF may be of benefit to cardiovascular function in ischemic cardiomyopthy.

Address correspondence to: Dr. Hongkui Jin, Department of Cardiovascular Research, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080. E-mail address: hkj{at}gene.com

This article has been cited by other articles:

				K. R. Cho, J.-S. Choi, W. Hahn, D. S. Kim, J. S. Park, D. S. Lee, and K.-B. Kim Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model Eur. J. Cardiothorac. Surg., October 1, 2008; 34(4): 857 - 863. [Abstract] [Full Text] [PDF]

				R. R. Edelman Can MR Imaging Be Used to Determine the Efficacy of Gene Therapy in the Heart? Radiology, October 1, 2008; 249(1): 1 - 2. [Full Text] [PDF]

				N. A. Gude, G. Emmanuel, W. Wu, C. T. Cottage, K. Fischer, P. Quijada, J. A. Muraski, R. Alvarez, M. Rubio, E. Schaefer, et al. Activation of Notch-Mediated Protective Signaling in the Myocardium Circ. Res., May 9, 2008; 102(9): 1025 - 1035. [Abstract] [Full Text] [PDF]

				G. Athauda, A. Giubellino, J. A. Coleman, C. Horak, P. S. Steeg, M.-J. Lee, J. Trepel, J. Wimberly, J. Sun, A. Coxon, et al. c-Met Ectodomain Shedding Rate Correlates with Malignant Potential. Clin. Cancer Res., July 15, 2006; 12(14): 4154 - 4162. [Abstract] [Full Text] [PDF]

				W. Wojakowski, M. Tendera, A. Michalowska, M. Majka, M. Kucia, K. Maslankiewicz, R. Wyderka, A. Ochala, and M. Z. Ratajczak Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ Stem Cells, and Mononuclear Cells Expressing Early Cardiac, Muscle, and Endothelial Markers Into Peripheral Blood in Patients With Acute Myocardial Infarction Circulation, November 16, 2004; 110(20): 3213 - 3220. [Abstract] [Full Text] [PDF]

				M. Borowiak, A. N. Garratt, T. Wustefeld, M. Strehle, C. Trautwein, and C. Birchmeier Met provides essential signals for liver regeneration PNAS, July 20, 2004; 101(29): 10608 - 10613. [Abstract] [Full Text] [PDF]