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EFFORTS OF UNIVERSITY OF TSUKUBAEfforts of University of Tsukuba

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Project

Investigation of the Molecular Mechanism of Aortic Aneurysms and Identification of Target Molecules for New Therapy

Summary

An aortic aneurysm is a malady in which the wall of the blood vessel dilates abnormally, leading to rupture, and eventually, death. Because the underlying mechanisms for this disease is not known, there is no effective drug therapies. Therefore, to clarify the molecular mechanisms of aortic aneurysm and to develop prevention and treatment strategies are an urgent task.

 

We have previously found that deficiency in fibulin-4, an extracellular matrix protein that controls vascular elasticity (the ability of expanded blood vessels to contract), induces aortic aneurysms (Huang et al. Circ. Res., 2010). Additionally, we found various pathological changes, including arterial wall thickening, elastic fiber disruption, vascular smooth muscle proliferation and local increase in renin-angiotensin signals at aortic aneurysm lesions (Huang et al. Sci. Transl. Med., 2013). Furthermore, by combining proteomic analysis, which is a comprehensive examination of protein expression, with biochemical and histological approaches, we identified that activation of the slingshot-cofilin pathway may be a new target molecule for aortic aneurysm therapy (Yamashiro et al. Sci. Signal., 2015).

 

Our study identified the signaling pathways involved in aortic aneurysm progression. We expect to develop new targets for drug discovery. Moving forward, we will develop inhibitors of these molecules, clarify the relationship between elastic fiber formation and vascular wall maintenance, with the goal of clinical application.

 

University of Tsukuba PR (featured research)
http://www.tsukuba.ac.jp/attention-research/p201510210300.html

QLife Pro medical news
http://www.qlifepro.com/news/20151023/identify-the-signaling-pathways-involved-in-the-formation-of-aortic-aneurysm.html

Santen Medical Channel
https://www.santen.co.jp/medical-channel/op/medicalnews/2015/1023-identify-the-signaling-pathways-involved-in-the-formation-of-aortic-aneurysm.html

 

Main member

YANAGISAWA Hiromi

Professor, Life Science Center for Survival Dynamics

YAMASHIRO Yoshito

Assistant Professor, Life Science Center for Survival Dynamics

HIRAMATSU Yuji

Professor, Cardiovascular Surgery, Faculty of Medicine

NAGAYAMA Kazuaki

Professor, College of Engineering, Ibaraki University

NAKAMURA Tomoyuki

Professor, Pharmacology, Kansai Medical University

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