Development of novel therapy for postpartum cardiomyopathy based on the comprehensive analysis of animal model and clinical gene sample

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09543
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: OTANI KENTARO 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (50470191)
• Co-Investigator(Kenkyū-buntansha): 徳留 健 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (00443474) ; 神谷 千津子 国立研究開発法人国立循環器病研究センター, 病院, 医長 (10551301)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 周産期心筋症 / ナトリウム利尿ペプチド / 授乳 / 心肥大

Outline of Final Research Achievements

In our previous work, we demonstrated that mice lacking guanylyl cyclase-A (GC-A), a receptor for atrial and brain natriuretic peptides, show severe postpartum cardiac hypertrophy and dysfunction similar to postpartum cardiomyopathy (PPCM). Additionally, two weeks of lactation significantly increased the plasma aldosterone level in GC-A-knockout mice (GC-A-KO), but not in wild-type mice. Here, we examined the mechanisms underlying the lactation-induced and aldosterone-dependent cardiac hypertrophy in GC-A-KO. In GC-A-KO heart, the IL-6 mRNA level was significantly upregulated during lactation. Additionally, weekly intraperitoneal injection of anti-IL-6 receptor antibody tended to suppress the lactation-induced cardiac hypertrophy in GC-A-KO. Taken together, our data implied that natriuretic peptides, aldosterone receptor antagonist, and anti-interleukin-6 receptor antibody have potential to be therapeutic agents for PPCM.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

周産期心筋症は心疾患既往のない女性が妊娠・産褥期に心不全を発症し、拡張型心筋症に類似した病態を呈する疾患であり、現状では疾患特異的な診断および治療法は存在しない。本研究の結果、周産期心筋症の新たな治療標的となり得る生体内のシグナル経路を特定するとともに、周産期心筋症の発症予測に応用可能な遺伝子多型を見出すことができた。今後、本研究成果を基にした周産期心筋症に対する疾患特異的な診断・治療法の開発が期待される。