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Comments for:

Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF
Teruya Nakamura, … , Hikaru Matsuda, Toshikazu Nakamura
Teruya Nakamura, … , Hikaru Matsuda, Toshikazu Nakamura
Published December 15, 2000
Citation Information: J Clin Invest. 2000;106(12):1511-1519. https://doi.org/10.1172/JCI10226.
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Article

Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF

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Abstract

Using a rat model of ischemia/reperfusion injury, we demonstrate here that HGF is cardioprotective due to its antiapoptotic effect on cardiomyocytes. Following transient myocardial ischemia and reperfusion, c-Met/HGF receptor expression rapidly increased in the ischemic myocardium, an event accompanied by a dramatic increase in plasma HGF levels in the infarcted rats. When endogenous HGF was neutralized with a specific antibody, the number of myocyte cell deaths increased markedly, the infarct area expanded, and the mortality increased to 50%, as compared with a control group in which there was no mortality. Plasma from the myocardial infarcted rats had cardioprotective effects on primary cultured cardiomyocytes, but these effects were significantly diminished by neutralizing HGF. In contrast, recombinant HGF administration reduced the size of infarct area and improved cardiac function by suppressing apoptosis in cardiomyocytes. HGF rapidly augmented Bcl-xL expression in injured cardiomyocytes both in vitro and in vivo. As apoptosis of cardiomyocytes is one of the major contributors to the pathogenesis in subjects with ischemia/reperfusion injury, prevention of apoptosis may prove to be a reasonable therapeutic strategy. Supplements of HGF, an endogenous cardioprotective factor, may be found clinically suitable in treating subjects with myocardial infarction.

Authors

Teruya Nakamura, Shinya Mizuno, Kunio Matsumoto, Yoshiki Sawa, Hikaru Matsuda, Toshikazu Nakamura

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HGF: A possible therapy for cerebral ischaemia/reperfusion injury?

Submitter: David Gurwitz | gurwitz@post.tau.ac.il

Tel-Aviv University

Published February 26, 2001

The authors of this elegant study conclude that pre-clinical and clinical trials of hepatocyte growth factor (HGF) for treatment of patients with myocardial infarction should be considered [1]. Indeed there is now hope, in view of the compelling new data, that such treatment might reduce the ischaemic damage to cardiomyocytes in the critical hours immediately following cardiac stroke. This might be a good time to note that the neuroprotective potential of HGF for treating individuals against cerebral ischaemia/reperfusion injury should also be more vigorously pursued. Five years ago, studies from the same lab [2] reported that HGF prolonged the survival of embryonic hippocampal neurons in primary culture. Moreover, transcription of both HGF and its receptor was markedly increased in response to middle cerebral artery occlusion mediated cerebral ischaemic injury, suggesting that HGF was an endogenous neurotrophic factor up-regulated following traumatic brain events. These observations were later verified at the protein level [3].
In addition, HGF was found to be elevated in Alzheimer's disease brains [4] suggesting that its transcription was also up-regulated during chronic neuronal degeneration. Unfortunately, very little progress has since been made with respect to the neurotrophic potential of HGF for treating cerebral ischaemia/reperfusion injury, another leading cause of human death and morbidity. It is hoped that the new study on its potential in cardiac ischaemia would also stimulate more research into the neuroprotective potential of HGF.
1. Nakamura T, Mizuno S, Matsumoto K, Sawa Y, Matsuda H and Nakamura T (2000). Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF. JCI 106:1511-1519
2. Honda S, Kagoshima M, Wanaka A, Tohyama M, Matsumoto K, Nakamura T (1995). Localization and functional coupling of HGF and c-Met/HGF receptor in rat brain: implication as neurotrophic factor. Brain Res Mol Brain Res 32:197-210
3. Hayashi T, Abe K, Sakurai M, Itoyama Y (1998) Inductions of hepatocyte growth factor and its activator in rat brain with permanent middle cerebral artery occlusion. Brain Res. 799:311-316.
4.Fenton H, Finch PW, Rubin JS, Rosenberg JM, Taylor WG, Kuo-Leblanc V, Rodriguez-Wolf M, Baird A, Schipper HM, Stopa EG. (1998) Hepatocyte growth factor (HGF/SF) in Alzheimer's disease. Brain Res. 779:262-270

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