Introduction

Although some therapeutic approaches for cardiovascular diseases have been improved during last decade or two, numerous problems and questions are remained unsolved. Our laboratory has a broad range of project from basic science to clinical research regarding cardiovascular diseases. Our goal is to understand the pathophysiology of cardiovascular diseases profoundly, and to harness the knowledge to develop into therapeutic use. Our laboratory welcome anyone who have enthusiasm and commitment for the cardiovascular research 

Research Projects

1. Regenerative medicine

Our goal is to find new therapeutic methods for ischemic cardiovascular diseases. Angiogenesis, growth of new blood vessels, is intriguing and dramatic phenomenon in development and pathological conditions of human body. Augmentation of angiogenesis is an important and promising strategy for ischemic cardiovascular diseases. We have reported the angiogenic effect of bone marrow cells in the disease models of animal experiments, then been trying to treat the patients with critical limb ischemia (CLI) by the new method using autologous bone marrow cells to relieve them from severe pain and rescue the limb from tissue loss. We have also been investigating to evaluate the regenerative effects of adipose-derived regenerative cells (ADRCs) for ischemic tissue in animal models. Then, we have started therapeutic angiogenesis for patients with CLI using ADRCs, as a clinical pilot study. Moreover, adipose tissue started attracting considerable attention in the health problems of modern life. We are interested in the factors secreted from fat tissue including adiponection and plan to apply the factors to the treatment of cardiovascular diseases.

2. Heart failure

We are conducting researches on heart failure and cardiomyopathy. Heart failure is one of the major leading causes of death all over the world, and it is becoming a big social burden as the aging progresses. We are actively participating not only in prospective observational studies but also in interventional multicenter clinical trials. In addition, we are clarifying challenges of management for heart failure and promoting return to comprehensive team medical care. On the other hand, the causes have not been established in many kinds of myocardial diseases. In severe cases, advanced treatment such as assistant artificial heart and heart transplant is needed. We have conducted molecular biological researches using blood and cardiac muscle tissue samples in addition to clinical studies using echocardiography, MRI and nuclear medicine examinations. The members of our group are approaching the clarification of pathological mechanisms from both the fundamental and clinical aspects.

3. Arrhythmia

Our electrophysiology team provides leading-edge treatments to patients with cardiac arrhythmias. We are able to offer a wide range of electrophysiological procedures: radiofrequency catheter ablation therapy, implantation of pacemaker and implantable cardioverter defibrillator (ICD), in addition to biventricular devices (cardiac resynchronization therapy; CRT, CRT-D); approximately 500 radiofrequency catheter ablation therapies and 100 high volume device therapies to the various cases in a year. We are currently participating in clinical and basic research studies in the following areas:Analysis of cardiac arrhythmias (e.g. Brugada syndrome) using electrocardiogram examination (e.g. QT interval): 12-lead electrocardiogram, special 24-hour electrocardiogram, late potential detection using signal-averaging electrocardiography. Indication criteria of CRT for severe cardiac failure patients.

4. Ischemic heart disease

Plaques of culprit lesions in patients with acute coronary syndrome are not necessarily those with severe stenosis but are often vulnerable plaques with mild to moderate stenosis, which contain numerous inflammatory cells and inflammation. In addition, large lipid cores and thin fibrous cap are considered to be typical histological markers for such plaques.Recently, it has been suggested that the tissue components of coronary plaque are detected by an integrated backscatter intravascular ultrasound and that thickness of fibrous-cap is analyzed by optical coherence tomography. Furthermore, multi-detector computed tomography, which is less invasive compared to catheter-related devices, can make high-resolution imaging of coronary artery and components of the coronary plaque. These modalities provide us useful coronary plaque information. Until now, we have reported many papers regarding detection of coronary plaque characterizations by using such useful techniques. For example, we have found that subjects with metabolic syndrome and/or impaired renal function are strongly related to higher lipid volume and lower fibrous volume in coronary plaques, which are associated with vulnerable plaques. Our findings may explain why such subjects have an increasing risk of cardiovascular event including acute coronary syndrome. Also, we have already found that intensive medical cares can change vulnerable plaques to stable ones. These findings may contribute reduction of newly onset of acute coronary syndrome, a life-threatening disease. From our experiences, we can provide suggestions for optimal therapy including life-style changing and pharmacological treatment to patients with ischemic heart disease.

Faculty Members

Faculty	Position	Department
Toyoaki Murohara	Professor	Cardiology
Yasuya Inden	Associate Professor	Cardiology
Yasuko Bando	Associate Professor	Cardiology
Hideki Ishii	Associate Professor	Cardiology
Kazuhisa Kondo	Associate Professor	Cardiology
Mikito Takefuji	Associate Professor	Cardiology
Kazumasa Unno	Associate Professor	Cardiology
Takahiro Okumura	Associate Professor	Advanced Heart Failure Center
Susumu Suzuki	Associate Professor	Cardiology
Ryo Hayashida	Associate Professor	Cardiology

Bibliography

• 2017

  1. Yanagisawa S, Inden Y, Kato H, Fujii A, Mizutani Y, Ito T, Kamikubo Y, Kanzaki Y, Ando M, Hirai M, Shibata R and Murohara T. Impaired renal function is associated with recurrence after cryoballoon catheter ablation for paroxysmal atrial fibrillation: A potential effect of non-pulmonary vein foci. J Cardiol. 2017;69:3-10.

• 2016

  1. Morimoto R, Okumura T, Bando YK, Fukaya K, Sawamura A, Kawase H, Shimizu S, Shimazu S, Hirashiki A, Takeshita K and Murohara T. Biphasic Force-Frequency Relation Predicts Primary Cardiac Events in Patients With Hypertrophic Cardiomyopathy. Circ J. 2016.
  2. Kawase H, Bando YK, Nishimura K, Aoyama M, Monji A and Murohara T. A dipeptidyl peptidase-4 inhibitor ameliorates hypertensive cardiac remodeling via angiotensin-II/sodium-proton pump exchanger-1 axis. J Mol Cell Cardiol. 2016;98:37-47.
  3. Morimoto R, Okumura T, Bando YK, Fukaya K, Sawamura A, Kawase H, Shimizu S, Shimazu S, Hirashiki A, Takeshita K and Murohara T. Biphasic Force-Frequency Relation Predicts Primary Cardiac Events in Patients With Hypertrophic Cardiomyopathy. Circ J. 2016.
  4. Kawase H, Bando YK, Nishimura K, Aoyama M, Monji A and Murohara T. A dipeptidyl peptidase-4 inhibitor ameliorates hypertensive cardiac remodeling via angiotensin-II/sodium-proton pump exchanger-1 axis. J Mol Cell Cardiol. 2016;98:37-47.
  5. Tanaka A, Ishii H, Suzuki S, Ota T, Oshima H, Usui A, Komori K and Murohara T. Influence of False Lumen Status on the Prognosis of Acute Type A Aortic Dissection without Urgent Surgical Treatment. J Atheroscler Thromb. 2016.

• 2015

  1. Yamamoto T, Shimano M, Inden Y, Takefuji M, Yanagisawa S, Yoshida N, Tsuji Y, Hirai M and Murohara T. Alogliptin, a dipeptidyl peptidase-4 inhibitor, regulates the atrial arrhythmogenic substrate in rabbits. Heart Rhythm. 2015;12:1362-9.

• 2014

  1. Osugi N, Suzuki S, Ishii H, Yasuda Y, Shibata Y, Tatami Y, Ota T, Kawamura Y, Okumura S, Tanaka A, Inoue Y, Matsuo S and Murohara T. Impact of albuminuria on the incidence of periprocedural myocardial injury in patients undergoing elective coronary stent implantation. Am J Cardiol. 2014;114:42-6.

• 2013

  1. Kito T, Shibata R, Ishii M, Suzuki H, Himeno T, Kataoka Y, Yamamura Y, Yamamoto T, Nishio N, Ito S, Numaguchi Y, Tanigawa T, Yamashita JK, Ouchi N, Honda H, Isobe K and Murohara T. iPS cell sheets created by a novel magnetite tissue engineering method for reparative angiogenesis. Sci Rep. 2013;3:1418.
  2. Shigeta T, Aoyama M, Bando YK, Monji A, Mitsui T, Takatsu M, Cheng XW, Okumura T, Hirashiki A, Nagata K and Murohara T. Dipeptidyl peptidase-4 modulates left ventricular dysfunction in chronic heart failure via angiogenesis-dependent and -independent actions. Circulation. 2012;126:1838-51.

• 2012

  1. Shimizu Y, Shibata R, Shintani S, Ishii M and Murohara T. Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells. J Am Heart Assoc. 2012;1:e000877.

• 2011

  1. Miyake H, Maeda K, Asai N, Shibata R, Ichimiya H, Isotani-Sakakibara M, Yamamura Y, Kato K, Enomoto A, Takahashi M and Murohara T. The actin-binding protein Girdin and its Akt-mediated phosphorylation regulate neointima formation after vascular injury. Circ Res. 2011;108:1170-9.

• 2009

  1. Kondo K, Shintani S, Shibata R, Murakami H, Murakami R, Imaizumi M, Kitagawa Y and Murohara T. Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis. Arterioscler Thromb Vasc Biol. 2009;29:61-6.

• 2008

  1. Kitamura T, Asai N, Enomoto A, Maeda K, Kato T, Ishida M, Jiang P, Watanabe T, Usukura J, Kondo T, Costantini F, Murohara T and Takahashi M. Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin. Nat Cell Biol. 2008;10:329-37.

Regenerative medicine	angiogenesis, adipose-derived regenerative cells (ADRC), endothelial progenitor cell(EPC)
Heart failure	cardiomyopathy, cardiac transplantation, ventricular assist device(VAD)
Arrhythmia	catheter ablation, cardiac resynchronize therapy, implantable cardiac defibrillator
Ischemic heart disease	percutaneous coronary intervention (PCI), intravenous ultrasound(IVUS), Transcatheter Aortic Valve Implantation (TAVI)