Intracellular Calcium Signals Inhibiting the Progression of Pulmonary Arterial Hypertension

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461619
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Keio University
• Principal Investigator: UCHIDA Keiko 慶應義塾大学, 保健管理センター(日吉), 講師 (50286522)
• Co-Investigator(Renkei-kenkyūsha): YAMAGISHI Hiroyuki 慶應義塾大学, 医学部小児科, 教授 (40255500)
• Research Collaborator: MIKOSHIBA Katsuhiko ; SHIBATA Akimichi
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: Calcium Signal / Pulmonary Hypertension

Outline of Final Research Achievements

Inositol trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel. As we found the strong expression of the type 2 IP3R (IP3R2) in the pulmonary arterial smooth muscle cells (PASMCs), we investigated the contribution of IP3R2 to pathophysiology of PAH.
IP3R2 knockout (KO) mice treated with chronic hypoxia showed higher PA pressure and RV pressure than WT mice in echocardiography. RV hypertrophy and medial wall thickness of PASMCs were more severe in KO. There was significant decrease of TUNEL positive cells in KO, suggesting that apoptosis was reduced in KO PASMCs. Ca2+ imaging revealed that SOCE was enhanced in KO compared with WT. Taken together, chronic hypoxia-induced PAH was deteriorated in IP3R2 KO. The deletion of IP3R2 gene led to inhibition of apoptosis and enhanced SOCE in PASMCs, probably resulting in acceleration of the progression of PAH induced by chronic hypoxia.

Free Research Field

pediatric cardiology