Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
Circulation. 1997;95:2552-2558

This Article
Right arrow Full Text
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ono, K.
Right arrow Articles by Sasayama, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ono, K.
Right arrow Articles by Sasayama, S.

(Circulation. 1997;95:2552.)
© 1997 American Heart Association, Inc.


Articles

Enhanced Expression of Hepatocyte Growth Factor/c-Met by Myocardial Ischemia and Reperfusion in a Rat Model

Koh Ono, MD; Akira Matsumori, MD, PhD; Tetsuo Shioi, MD, PhD; Yutaka Furukawa, MD, PhD; Shigetake Sasayama, MD, PhD

the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.

Correspondence to Akira Matsumori, MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawaracho Shogoin, Sakyo-ku, Kyoto 606, Japan.

Abstract

Background Hepatocyte growth factor (HGF) is a multifunctional factor implicated in tissue regeneration, wound healing, and angiogenesis. Circulating HGF is reportedly elevated during the early stage of myocardial infarction. However, its precise effect on the heart is unknown. To evaluate the regulation of HGF in ischemically damaged myocardium, the production of HGF and its high-affinity receptor, c-Met, was studied in a rat model of myocardial ischemia and reperfusion.

Methods and Results The plasma concentration of HGF began to increase within 1 hour of reperfusion after 1 hour of ischemia. The peak level was reached at 3 hours after reperfusion. Northern blotting revealed that HGF mRNA expression in the heart was augmented threefold at 24 and 48 hours and remained elevated by twofold at 120 hours after the myocardium was reperfused. The signal for c-met , high-affinity HGF receptor mRNA, was also upregulated parallel to upregulation for HGF. In the kidney, liver, lung, and spleen, HGF mRNA was also maximally increased at 12 hours after reperfusion. However, c-met was not upregulated in these organs. Immunohistochemical studies disclosed that capillary endothelial and interstitial cells, including infiltrating macrophages, were intensely stained for HGF, whereas capillary endothelial cells in the reperfused myocardium were positive for c-Met.

Conclusions This study is the first to show that myocardial ischemia and reperfusion induced HGF expression in various organs in vivo. These results indicate that HGF/c-Met plays a role in capillary endothelial cell regeneration in the ischemically injured heart.


Key Words: hepatocyte growth factor • myocardial infarction • immunohistochemistry • collateral circulation • reperfusion




This article has been cited by other articles:


Home page
RadiologyHome page
M. Saeed, A. Martin, P. Ursell, L. Do, M. Bucknor, C. B. Higgins, and D. Saloner
MR Assessment of Myocardial Perfusion, Viability, and Function after Intramyocardial Transfer of VM202, a New Plasmid Human Hepatocyte Growth Factor in Ischemic Swine Myocardium
Radiology, October 1, 2008; 249(1): 107 - 118.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
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]


Home page
ANGIOLOGYHome page
J.-W. Lin, W. H.-H. Sheu, W.-J. Lee, Y.-T. Chen, T.-J. Liu, C.-T. Ting, and W.-L. Lee
Circulating Hepatocyte Growth Factor Level but Not Basic Fibroblast Growth Factor Level Is Elevated in Angiography-Proven Symptomatic Peripheral Artery Disease
Angiology, September 1, 2007; 58(4): 420 - 428.
[Abstract] [PDF]


Home page
J. Immunol.Home page
T. Ohnishi, K. Kakimoto, K. Bandow, C. J. Lowenstein, Y. Daikuhara, and T. Matsuguchi
Mature Hepatocyte Growth Factor/Scatter Factor on the Surface of Human Granulocytes Is Released by a Mechanism Involving Activated Factor Xa.
J. Immunol., June 1, 2006; 176(11): 6945 - 6953.
[Abstract] [Full Text] [PDF]


Home page
Stem CellsHome page
B.-R. Son, L. A. Marquez-Curtis, M. Kucia, M. Wysoczynski, A. R. Turner, J. Ratajczak, M. Z. Ratajczak, and A. Janowska-Wieczorek
Migration of Bone Marrow and Cord Blood Mesenchymal Stem Cells In Vitro Is Regulated by Stromal-Derived Factor-1-CXCR4 and Hepatocyte Growth Factor-c-met Axes and Involves Matrix Metalloproteinases
Stem Cells, May 1, 2006; 24(5): 1254 - 1264.
[Abstract] [Full Text] [PDF]


Home page
J. Thorac. Cardiovasc. Surg.Home page
Y. Shirakawa, Y. Sawa, Y. Takewa, E. Tatsumi, Y. Kaneda, Y. Taenaka, and H. Matsuda
Gene transfection with human hepatocyte growth factor complementary DNA plasmids attenuates cardiac remodeling after acute myocardial infarction in goat hearts implanted with ventricular assist devices
J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 624 - 632.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
M. E. Gerritsen
HGF and VEGF: A Dynamic Duo
Circ. Res., February 18, 2005; 96(3): 272 - 273.
[Full Text] [PDF]


Home page
Circ. Res.Home page
J.-K. Min, Y.-M. Lee, J. H. Kim, Y.-M. Kim, S. W. Kim, S.-Y. Lee, Y. S. Gho, G. T. Oh, and Y.-G. Kwon
Hepatocyte Growth Factor Suppresses Vascular Endothelial Growth Factor-Induced Expression of Endothelial ICAM-1 and VCAM-1 by Inhibiting the Nuclear Factor-{kappa}B Pathway
Circ. Res., February 18, 2005; 96(3): 300 - 307.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
Y. Cao, A. Hong, H. Schulten, and M. J. Post
Update on therapeutic neovascularization
Cardiovasc Res, February 15, 2005; 65(3): 639 - 648.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
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]


Home page
CirculationHome page
L. Lei, R. Zhou, W. Zheng, L. P. Christensen, R. M. Weiss, and R. J. Tomanek
Bradycardia Induces Angiogenesis, Increases Coronary Reserve, and Preserves Function of the Postinfarcted Heart
Circulation, August 17, 2004; 110(7): 796 - 802.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
S. Pikkarainen, H. Tokola, R. Kerkela, and H. Ruskoaho
GATA transcription factors in the developing and adult heart
Cardiovasc Res, August 1, 2004; 63(2): 196 - 207.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
R. M. Day, G. Thiel, J. Lum, R. D. Chevere, Y. Yang, J. Stevens, L. Sibert, and B. L. Fanburg
Hepatocyte Growth Factor Regulates Angiotensin Converting Enzyme Expression
J. Biol. Chem., March 5, 2004; 279(10): 8792 - 8801.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
V. Jayasankar, Y. J. Woo, L. T. Bish, T. J. Pirolli, S. Chatterjee, M. F. Berry, J. Burdick, T. J. Gardner, and H. L. Sweeney
Gene Transfer of Hepatocyte Growth Factor Attenuates Postinfarction Heart Failure
Circulation, September 9, 2003; 108(90101): II-230 - 236.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. Ding, T. Merkulova-Rainon, Z. C. Han, and G. Tobelem
HGF receptor up-regulation contributes to the angiogenic phenotype of human endothelial cells and promotes angiogenesis in vitro
Blood, June 15, 2003; 101(12): 4816 - 4822.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
Y. Li, G. Takemura, K.-i. Kosai, K. Yuge, S. Nagano, M. Esaki, K. Goto, T. Takahashi, K. Hayakawa, M. Koda, et al.
Postinfarction Treatment With an Adenoviral Vector Expressing Hepatocyte Growth Factor Relieves Chronic Left Ventricular Remodeling and Dysfunction in Mice
Circulation, May 20, 2003; 107(19): 2499 - 2506.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
D. J. Lenihan, A. Osman, V. Sriram, J. Aitsebaomo, and C. Patterson
Evidence for association of coronary sinus levels of hepatocyte growth factor and collateralization in human coronary disease
Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1507 - H1512.
[Abstract] [Full Text] [PDF]


Home page
Ann. Thorac. Surg.Home page
I. Ahmet, Y. Sawa, T. Yamaguchi, and H. Matsuda
Gene transfer of hepatocyte growth factor improves angiogenesis and function of chronic ischemic myocardium in canine heart
Ann. Thorac. Surg., April 1, 2003; 75(4): 1283 - 1287.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
N. Tomita, R. Morishita, Y. Taniyama, H. Koike, M. Aoki, H. Shimizu, K. Matsumoto, T. Nakamura, Y. Kaneda, and T. Ogihara
Angiogenic Property of Hepatocyte Growth Factor Is Dependent on Upregulation of Essential Transcription Factor for Angiogenesis, ets-1
Circulation, March 18, 2003; 107(10): 1411 - 1417.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
K. Kitta, R. M. Day, Y. Kim, I. Torregroza, T. Evans, and Y. J. Suzuki
Hepatocyte Growth Factor Induces GATA-4 Phosphorylation and Cell Survival in Cardiac Muscle Cells
J. Biol. Chem., February 7, 2003; 278(7): 4705 - 4712.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
C. Heeschen, S. Dimmeler, C. W. Hamm, E. Boersma, A. M. Zeiher, M. L. Simoons, and on Behalf of the CAPTURE (c7E3 Anti-Platelet Thera
Prognostic Significance of Angiogenic Growth Factor Serum Levels in Patients With Acute Coronary Syndromes
Circulation, February 4, 2003; 107(4): 524 - 530.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
H. Jin, R. Yang, W. Li, A. K. Ogasawara, R. Schwall, D. A. Eberhard, Z. Zheng, D. Kahn, and N. F. Paoni
Early Treatment with Hepatocyte Growth Factor Improves Cardiac Function in Experimental Heart Failure Induced by Myocardial Infarction
J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 654 - 660.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
M. Kinoshita, T. Miyamoto, N. Ohashi, S. Sasayama, and A. Matsumori
Thrombosis Increases Circulatory Hepatocyte Growth Factor by Degranulation of Mast Cells
Circulation, December 10, 2002; 106(24): 3133 - 3138.
[Abstract] [Full Text] [PDF]


Home page
J. Thorac. Cardiovasc. Surg.Home page
T. Funatsu, Y. Sawa, S. Ohtake, T. Takahashi, G. Matsumiya, N. Matsuura, T. Nakamura, and H. Matsuda
Therapeutic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor
J. Thorac. Cardiovasc. Surg., December 1, 2002; 124(6): 1099 - 1105.
[Abstract] [Full Text]


Home page
Cardiovasc ResHome page
I. M.C. Dixon
Help from within: cardioprotective properties of hepatocyte growth factor
Cardiovasc Res, July 1, 2001; 51(1): 4 - 6.
[Full Text] [PDF]


Home page
Cardiovasc ResHome page
H. Ueda, T. Nakamura, K. Matsumoto, Y. Sawa, H. Matsuda, and T. Nakamura
A potential cardioprotective role of hepatocyte growth factor in myocardial infarction in rats
Cardiovasc Res, July 1, 2001; 51(1): 41 - 50.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
S. Tateno, M. Terai, K. Niwa, T. Jibiki, H. Hamada, K. Yasukawa, T. Honda, S. Oana, and Y. Kohno
Alleviation of Myocardial Ischemia After Kawasaki Disease by Heparin and Exercise Therapy
Circulation, May 29, 2001; 103(21): 2591 - 2597.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
A. Kawamoto, H.-C. Gwon, H. Iwaguro, J.-I. Yamaguchi, S. Uchida, H. Masuda, M. Silver, H. Ma, M. Kearney, J. M. Isner, et al.
Therapeutic Potential of Ex Vivo Expanded Endothelial Progenitor Cells for Myocardial Ischemia
Circulation, February 6, 2001; 103(5): 634 - 637.
[Abstract] [Full Text] [PDF]


Home page
IOVSHome page
I. M. Wormstone, S. Tamiya, J. M. Marcantonio, and J. R. Reddan
Hepatocyte Growth Factor Function and c-Met Expression in Human Lens Epithelial Cells
Invest. Ophthalmol. Vis. Sci., December 1, 2000; 41(13): 4216 - 4222.
[Abstract] [Full Text]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
C. Haug, A. Schmid-Kotsas, U. Zorn, M. G. Bachem, S. Schuett, A. Gruenert, and E. Rozdzinski
Hepatocyte growth factor is upregulated by low-density lipoproteins and inhibits endothelin-1 release
Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2865 - H2871.
[Abstract] [Full Text] [PDF]


Home page
Ann. Thorac. Surg.Home page
K. Nishizaki, O. Mazda, Y. Dohi, T. Kawata, K. Mizuguchi, S. Kitamura, and S. Taniguchi
In vivo gene gun-mediated transduction into rat heart with Epstein-Barr virus-based episomal vectors
Ann. Thorac. Surg., October 1, 2000; 70(4): 1332 - 1337.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
S. Yasuda, Y. Goto, T. Baba, T. Satoh, H. Sumida, S. Miyazaki, and H. Nonogi
Enhanced secretion of cardiac hepatocyte growth factor from an infarct region is associated with less severe ventricular enlargement and improved cardiac function
J. Am. Coll. Cardiol., July 1, 2000; 36(1): 115 - 121.
[Abstract] [Full Text] [PDF]


Home page
IOVSHome page
W. Cai, S. L. Rook, Z. Y. Jiang, N. Takahara, and L. P. Aiello
Mechanisms of Hepatocyte Growth Factor-Induced Retinal Endothelial Cell Migration and Growth
Invest. Ophthalmol. Vis. Sci., June 1, 2000; 41(7): 1885 - 1893.
[Abstract] [Full Text]


Home page
HeartHome page
Y Zhu, Y Hojo, U Ikeda, K Shimada;, and G F BAXTER
Production of hepatocyte growth factor during acute myocardial infarction
Heart, April 1, 2000; 83(4): 450 - 455.
[Abstract] [Full Text]


Home page
J. Clin. Endocrinol. Metab.Home page
Y. Yoshitomi, S. Kojima, T. Umemoto, K. Kubo, Y. Matsumoto, M. Yano, T. Sugi, and M. Kuramochi
Serum Hepatocyte Growth Factor in Patients with Peripheral Arterial Occlusive Disease
J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2425 - 2428.
[Abstract] [Full Text]


Home page
Ann. Thorac. Surg.Home page
H. Ueda, Y. Sawa, K. Matsumoto, S. Kitagawa-Sakakida, Y. Kawahira, T. Nakamura, Y. Kaneda, and H. Matsuda
Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart
Ann. Thorac. Surg., June 1, 1999; 67(6): 1726 - 1731.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
S. Yasuda, Y. Goto, H. Sumida, T. Noguchi, T. Baba, S. Miyazaki, and H. Nonogi
Angiotensin-Converting Enzyme Inhibition Restores Hepatocyte Growth Factor Production in Patients With Congestive Heart Failure
Hypertension, June 1, 1999; 33(6): 1374 - 1378.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
R. Morishita, S. Nakamura, S.-i. Hayashi, Y. Taniyama, A. Moriguchi, T. Nagano, M. Taiji, H. Noguchi, S. Takeshita, K. Matsumoto, et al.
Therapeutic Angiogenesis Induced by Human Recombinant Hepatocyte Growth Factor in Rabbit Hind Limb Ischemia Model as Cytokine Supplement Therapy
Hypertension, June 1, 1999; 33(6): 1379 - 1384.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
F. Blanquaert, A. M. Delany, and E. Canalis
Fibroblast Growth Factor-2 Induces Hepatocyte Growth Factor/Scatter Factor Expression in Osteoblasts
Endocrinology, March 1, 1999; 140(3): 1069 - 1074.
[Abstract] [Full Text]


Home page
CirculationHome page
E. Van Belle, B. Witzenbichler, D. Chen, M. Silver, L. Chang, R. Schwall, and J. M. Isner
Potentiated Angiogenic Effect of Scatter Factor/Hepatocyte Growth Factor via Induction of Vascular Endothelial Growth Factor : The Case for Paracrine Amplification of Angiogenesis
Circulation, February 3, 1998; 97(4): 381 - 390.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
W. Schaper and T. Kubin
Is Hepatocyte Growth Factor a Protein With Cardioprotective Activity in the Ischemic Heart?
Circulation, June 3, 1997; 95(11): 2471 - 2472.
[Full Text]


Home page
J. Biol. Chem.Home page
M. Kimura, Y. Mizukami, T. Miura, K. Fujimoto, S. Kobayashi, and M. Matsuzaki
Orphan G Protein-coupled Receptor, GPR41, Induces Apoptosis via a p53/Bax Pathway during Ischemic Hypoxia and Reoxygenation
J. Biol. Chem., July 6, 2001; 276(28): 26453 - 26460.
[Abstract] [Full Text] [PDF]