Roles of soluble Flt-1 in renal dysfunction-related heart failure.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461115
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Nara Medical University
• Principal Investigator: TAKEDA YUKIJI 奈良県立医科大学, 医学部, 研究員 (60398443)
• Co-Investigator(Kenkyū-buntansha): SAITO Yoshihiko 奈良県立医科大学, 医学部第1内科, 教授 (30250260)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 心腎連関 / 可溶性Flt-1 / PLGF / 心不全 / 肺水腫

Outline of Final Research Achievements

Cardiac hypertrophy and heart failure are highly associated with chronic kidney diseases (CKD), by which mechanism is not fully understood.
The present study showed that production of PLGF is up-regulated and and a soluble form of its receptor, fms-like tyrosine kinase, is down-regulated in CKD.
Given that sFlt-1 acts as an endogenous antagonist against PLGF, the present study also provides the evidence that the imbalance of PLGF and sFlt-1production enhances the biological signaling pathway via Flt-1, and is involved in the cardiac hypertrophy and heart failure associated with CKD, via relative activation of the PLGF/Flt-1 pathway, using mice specifically lacking sFlt-1 but not Flt-1. These findings raise the possibility that the treatment strategy, inhibiting PLGF action or enhancing sFLt-1 production, is useful for the treatment of hypertrophy and heart failure in CKD.

Free Research Field

循環器内科