Pathophysiology of brain ischemia focused on ROS-producing enzyme Nox4 expressed in brain microvascular pericytes

2016 Fiscal Year Final Research Report

• Project/Area Number: 25461134
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kyushu University
• Principal Investigator: KURODA JUNYA 九州大学, 大学病院, 助教 (70614858)
• Research Collaborator: AGO Tetsuro ; NISHIMURA Ataru ; TACHIBANA Masaki
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: Nox4 / 脳血管周皮細胞 / 脳虚血 / 活性酸素 / Neurovascular Unit / 血液脳関門 / PDGFRβ / 脳梗塞治療

Outline of Final Research Achievements

Brain microvascular pericyte, one of the cells constituting neurovascular unit, plays a pivotal role in pathophysiology of brain ischemia. We have found that Nox4, an enzyme producing reactive oxygen species (ROS), was expressed in brain microvascular pericyte and that Nox4 was upregulated by some stimuli such as hypoxic condition and angiotensin II and was involved in proliferation of the cells. In brain ischemia, Nox4 was associated with breakdown of blood-brain barrier and enlargement of the infarct, and activation of NFκB and MMP9 was important as its mechanism. We also raised the possibility that in ischemic conditions, basic FGF could be involved in upregulation of PDGFRβ, a protein playing a role in pericyte function. Nox4 in brain pericytes could be a potential target for new therapies of cerebrovascular diseases.

Free Research Field

脳血管障害