Cardiovascular Medicine, Vascular Biology, Regenerative Medicine

Education

Kumamoto University, School of Medicine, M.D. 1985 Kumamoto University, Graduate School of Medicine, Ph.D. 1992 Jefferson Medical College, Dept. of Physiology Post. Doc. 1996 Tufts University, St. Elizabeth’s Medical Center, Post. Doc. 1997

Professional Experience

1985-1987 Intern

Kumamoto University School of Medicine
Division of Cardiology, Kumamoto, Japan

1987-1988 Resident

National Kumamoto Hospital
Department of Internal medicine, Kumamoto, Japan

1992-1993 Fellow

Saiseikai Kumamoto Hospital
Division of Cardiology, Kumamoto Japan

1993-1996 Postdoctoral Fellow

Thomas Jefferson University
Department of Physiology, Philadelphia, PA

1996-1997 Postdoctoral Fellow

Tufts University School of Medicine
St Elizabeth’s Medical Center
Department of Cardiology, Boston, MA

1997-2002 Assistant Professor

Kurume University School of Medicine
The Cardiovascular Research Institute, and
Department of Internal Medicine III

2002-current Professor

Nagoya University Graduate School of Medicine
Department of Cardiology

Suppression of tumor growth and atherogenesis by regulation of angioneurogenesis

Tumor growth requires neovascularization, and angiogenesis inhibitors have been shown to reduce tumor growth and metastasis, called “tumor dormancy therapy”. Likewise, neovascularization within the intima of atherosclerotic lesions has been shown to promote atherosclerotic plaque growth. Prolonged treatment with angiogenesis inhibitors could reduce plaque growth and intimal neovascularization in atherosclerosis-prone apoE -/- mice. In this regard, both tumorigenesis and plaque growth are the “Broad Mandate of Angiogenesis”.

Meanwhile, it has been well documented that peripheral nerve endings densely distribute within the adventitia of vessels. Mukouyama et al. previously demonstrated that sensory nerves could determine the pattern of blood vessel branching. Considering the fact that intra-plaque angiogenesis arise from the Vasa Vasorum, adventitial neurogenesis would be able to modify Vaso Vasorum angiogenesis thereby regulate plaque growth via an angiogenesis-dependent manner. Similarly, neurogenesis would modulate angiogenesis in and around tumors and could control tumor growth and metastasis.

However, the roles of neurogenesis in tumor growth and atherogenic plaque progression are largely unknown so far. Accordingly, in the present research, we sought to investigate the role of both neurogenesis and angiogenesis (angioneurogenesis) in the development of atherosclerotic plaque progression and tumor biology.

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1. Ishii H et al. Pharmacological intervention for prevention of left ventricular remodeling and improving prognosis in myocardial infarction. Circulation in press (2008)
2. Kitamura T et al. Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate girdin. Nature Cell Biol. 10: 329-337 (2008)
3. Nakamura T et al. Significance and Therapeutic Potential of Endothelial Progenitor Cell Transplantation in a Cirrhotic Liver Rat Model. Gastroenterology 133: 91-107 (2007)
4. Cheng XW et al. Mechanisms underlying the impairment of ischemia-induced neovascularization in MMP-2-deficient mice. Circ. Res. 100: 904-913 (2007)
5. Numaguchi Y et al. The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction. Circulation 114: I114-I119 (2006)
6. Shintani S et al. Synergistic effect of combined intramyocardial CD34 cells and VEGF-2 gene therapy post-myocardial infarction. Nature Clin. Pract. Cardiovasc. Med. 3: S123-S128 (2006)
7. Egami K et al. Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth. J. Clin. Invest. 112: 67-75 (2003)
8. Tateishi-Yuyama E et al. for the Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 360: 427-435 (2002)
9. Sasaki K et al. Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis. J Clin Invest. 109: 603-611 (2002)
10. Kamihata H et al. Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation 104: 1046-1052 (2001)
11. Shintani S et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103: 2776-2779 (2001)
12. Shintani S et al. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation 103: 897-903 (2001)
13. Murohara T et al. Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest. 105: 1527-1536 (2000)
14. Murohara T et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest. 101: 2567-2578 (1998)
15. Murohara T et al. Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin. Circulation 97: 99-107 (1998)
16. Murohara T et al. Reciprocal relation between VEGF and NO in the regulation of endothelial integrity. Nature Med. 3: 879-886 (1997)
17. Asahara T et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 275: 964-967 (1997)
18. Buerke M et al. Cardioprotective effect of insulin-like growth factor I in myocardial ischemia and reperfusion. Proc. Natl. Acad. Sci. USA. 92: 8031-8035 (1995)

Irvine H. Page Award. American Heart Association (AHA), Annual Scientific Sessions 1997, November 9-12,1997, Orlando, Florida. Title: Reciprocal relationship between vascular endothelial growth factor and nitric oxide in the regulation of endothelial integrity.

Young Investigators Award, American College of Cardiology, The 49th Annual Scientific Sessions. March 12-15, 2000, Anaheim, CA. Title: Augmentation of postnatal neovascularization by transplantation of cord blood-derived endothelial progenitor cells.

Press Conference

American Heart Association (AHA), Scientific Sessions 1999, November 7-10, 1999. Atlanta, GA. Murohara T. Heterologous transplantation of human cord blood-derived endothelial progenitor cells participate in postnatal angiogenesis in vivo. CNN, BBC On line. http://news.bbc.co.uk/1/hi/health/510072.stm