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J Thorac Cardiovasc Surg 2007;133:1120
© 2007 The American Association for Thoracic Surgery

Letter to the Editor

Which cell is transferred hepatocyte growth factor gene?

Masahiro Sakurai, MD, PhD

Department of Cardiovascular Surgery, National Hospital Organization Sendai Medical Center, Sendai, Japan

To the Editor:

I read with interest the article by Shi and associates,1Go titled "Nonviral Gene Transfer of Hepatocyte Growth Factor Attenuates Neurologic Injury After Spinal Cord Ischemia in Rabbits." It is already known that hepatocyte growth factor (HGF) functions as a powerful angiogenic factor, as well as a potent neurotrophic factor,2Go and HGF is not expressed in the spinal cord in the early phase after the ischemia.3Go Thus I agree that gene transfer of HGF could induce tolerance against a severe spinal cord ischemic insult. Furthermore, intrathecal injection of HGF gene is less invasive than viral injection to the spinal cord. However, I have one question. The authors have not demonstrated that HGF was induced in any cells. Johnson and associates4Go demonstrated that flunarizine has a protective effect on neurologic recovery after spinal cord ischemia, and the mechanism of protection involves inhibition of calcium accumulation rather than a direct effect on vascular smooth muscle using spinal cord blood flow measurements. Furthermore, Hayashi and associates5Go demonstrated that prevention of delayed CA1 neuronal death after cerebral ischemia in the gerbil by subarachnoid HGF gene transfer is due to the inhibition of apoptosis through the blockade of Bax translocation from the cytoplasm to the nucleus. These results suggest that HGF gene into intrathecal injection may have a protective effect against neuronal apoptotic cascade rather than angiogenic effect. Therefore, to elucidate the mechanism of neuronal protection, the authors should demonstrate temporal profiles of HGF in histochemical study or in in situ hybridization study.

References

  1. Shi E, Jiang X, Kazui T, Washiyama N, Yamashita K, Terada H, et al. Nonviral gene transfer of hepatocyte growth factor attenuates neurologic injury after spinal cord ischemia in rabbits. J Thorac Cardiovasc Surg 2006;132:941-947.[Abstract/Free Full Text]
  2. Korhonen L, Sjoholm U, Takei N, Kern MA, Schirmacher P, Castren E, et al. Expression of c-Met in developing rat hippocampus: evidence for HGF as a neurotrophic factor for calbindin D-expressing neurons. Eur J Neurosci 2000;12:3453-3461.[Medline]
  3. Hayashi T, Sakurai M, Abe K, Sadahiro M, Tabayashi K. Expressions of VEGF and bFGF in rabbit spinal cord after transient ischemia. Neuropathol Appl Neurobiol 1999;25:63-71.[Medline]
  4. Johnson SH, Kraimer JM, Graeber GM. Effects of flunarizine on neurological recovery and spinal cord blood flow in experimental spinal cord ischemia in rabbits. Stroke 1993;24:1547-1553.[Abstract/Free Full Text]
  5. Hayashi K, Morishita R, Nakagami H, Yoshimura S, Hara A, Matsumoto K, et al. Gene therapy for preventing neuronal death using hepatocyte growth factor: in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CA1 neurons. Gene Ther 2001;8:67-73.[Medline]

Related Article

Reply to the Editor
Enyi Shi
J. Thorac. Cardiovasc. Surg. 2007 133: 1120-1121. [Extract] [Full Text] [PDF]




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