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Cardiovascular Research

Master's Program -
Doctor's Program -

Staff List

Professor SHINDO Takayuki
Associate Professor SAKURAI Takayuki
Assistant Professor KAMIYOSHI Akiko

Contact

E-mail : organregen-1(at)shinshu-u.ac.jp
※ Change (at) to @ when you send an e-mail.

Summary of Activity

 We are studying the mechanisms of diseases such as atherosclerosis, hypertension, and organ dysfunctions, and developing new therapies.  We have succeeded in generating original genetically-engineered animal models and are working vigorously on molecular medicine and therapeutics using these models.

 Our laboratory is the newest at Shinshu University but we are the only laboratory that can handle the entire course of planning, generating, and analysis of original gene-engineered mice. Experience with us the excitement of new discoveries that may very well become novel therapies for diseases.

Research Subject

To develop new therapies, we must employ various techniques that are available to today’s medical science (not only animal experiments, but also gene-engineering, biochemistry, physiology, and pathology). Our students learn various important techniques used in medical science, as well as how to manipulate ES-cells and embryos.

 

Research themes of our laboratory are as follows;

1. Developing novel therapy by using models of atherosclerosis, hypertension, heart failure, renal failure, and liver dysfunction.

2. Pathophysiological analysis of vasoactive peptides and their receptors

3. Therapeutic angiogenesis

4. Developing novel techniques in gene-engineering and embryo-manipulation. Generation and analysis of new models.

 

  For example, I want to describe adrenomedullin (AM)-knockout mice, which we generated.  AM was originally identified as a vasodilating peptide. By generating AM-knockout mice, we first found that they are embryonic lethal with severe hemorrhage and edema (See figures).  This is because the vascular structure of AM-knock out mouse embryos is fragile.  We found that AM is a novel angiogenic factor, which is necessary for vascular stability.  Studies using AM are currently underway for the new technique of therapeutic angiogenesis.



Major Publications

1. Koyama T, Ochoa-Callejero L, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Iinuma N, Arai T, Yoshizawa T, Iesato Y, Lei Y, Uetake R, Okimura A, Yamauchi A, Tanaka M, Igarashi K, Toriyama Y, Kawate H, Adams R.H, Kawakami H, Mochizuki N, Martínez A, Shindo T.
Vascular endothelial adrenomedullin-RAMP2 system is essential for vascular integrity and organ homeostasis
Circulation. 127(7) 842-53. 2013

2. Yoshizawa T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Iesato Y, Koyama T, Uetake R, Yang L, Yamauchi A, Tanaka M, Toriyama Y, Igarashi K, Nakada T, Kashihara T, Yamada M, Kawakami H, Nakanishi H, Taguchi R, Nakanishi T, Akazawa H, Shindo T.
Novel regulation of cardiac metabolism and homeostasis by the adrenomedullin-RAMP2 system
Hypertension. 61(2) 341-51. 2013

3. Iesato Y, Toriyama Y, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Yoshizawa T, Koyama T, Uetake R, Yang L, Yamauchi A, Tanaka M, Igarashi K, Murata T, Shindo T.
Adrenomedullin-RAMP2 system is crucially involved in retinal angiogenesis
Am J Pathol. 182(6) 2380-90. 2013

4. Yang L, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Yoshizawa T, Koyama T, Iesato Y, Uetake R, Yamauchi A, Tanaka M, Toriyama Y, Igarashi K, Shindo T.
Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury
J Mol Cell Cardiol. 59C:55-66. 2013

5. Shindo T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Shimoyama N, Iinuma N, Arai T, Miyagawa S.
Regulation of adrenomedullin and its family peptide by RAMP system
Curr Prot Pept Sci. (in press) 2013

6. Shindo T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y.
Adrenomedullin-RAMP2 system in cardiovascular development and homeostasis
Curr Hypertens Rev. 7 (4) 217-27. 2011

7. Arai T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Iinuma N, Iesato Y, Koyama T, Yoshizawa T, Uetake R, Yamauchi A,  Yang L, Kawate H, Ogawa S, Kobayashi A, Miyagawa S, Shindo T.
Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling
Peptides. 32(9) 1855-65. 2011

8. Iinuma N, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Arai T, Yoshizawa T, Koyama T, Uetake R, Kawate H, Muto S, Tagawa Y, Miyagawa S, Shindo T.
Adrenomedullin in sinusoidal endothelial cells play protective roles against cold injury of liver.
Peptides.  31(5) 865-71. 2010 

9. Kamiyoshi A, Sakurai T, Ichikawa-Shindo Y. Iinuma N, Kawate H, Yoshizawa T, Koyama T, Muto S, Shindo T.
Endogenous a-CGRP mitigates liver fibrosis in chronic hepatitis induced by repeated administration of concanavalin A.
Liver International. 29 (5) 642-9. 2009 

10. Ichikawa-Shindo Y, Sakurai T, Kamiyoshi A, Kawate H, Iinuma N, Yoshizawa T, Koyama T, Fukuchi J, Iimuro S, Moriyama N, Kawakami H, Murata T, Kangawa K, Nagai R, Shindo T. 
GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity. 
J Clin Invest. 118, 29-39. 2008

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