Integrin Overexpression Improves sepsis-induced myocardial injury through attenuation of ER Stress

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K17047
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Gifu University
• Principal Investigator: Kawaguchi Tomonori 岐阜大学, 医学部附属病院, 助教 (40456504)
• Research Collaborator: Ross Robert S.
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 敗血症性心筋障害

Outline of Final Research Achievements

Alterations in calcium homeostasis in the endoplasmic/sarcoplasmic reticulum (ER) can cause stress that ultimately may affect ventricular function. Previous report showed that α7β1D integrin modified Ca2+ regulatory pathways in the cardiomyocyte via ryanodine receptor 2 (RyR2) stabilization. In the present study, we hypothesized that integrin overexpression (OE) would have beneficial effects against sepsis-induced myocardial injury via the inhibition of ER stress.LPS injected to 9-12 week old α7β1D integrin overexpressing male mice and age/gender-matched littermate controls. These mice were sacrificed 48 hours after LPS injection.
Integrin α7β1D OE did not alter expression of Ca2+ transport proteins (SERCA2a, NCX-1 or RyR2) but did reduce RyR2 phosphorylation at serine 2808. eIF2a-P and CRT were significantly decreased in α7β1D integrin OE mice. These results suggest that α7β1D integrin OE decreases ER stress in sepsis-induced myocardial injury.

Free Research Field

救急集中治療

Academic Significance and Societal Importance of the Research Achievements

敗血症による心機能の低下は40%-50%の患者に見られ、死亡率の悪化が示唆されている一方でその心筋障害は可逆的であり、7-10日で回復するとされており、明確な原因は解明されておらず、治療法も確立していない。
本研究において心機能障害を改善することが敗血症自体の予後を大きく変わることが確認できたため、敗血症時に心保護をすることの重要性が注目されるようになると考えられた。