Analysis for biomarkers derived from placenta in postpartum cardiomyopathy with preeclampsia

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16756
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Shimizu Takashi 東京大学, 医学部附属病院, 登録研究員 (00792061)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 周産期心筋症

Outline of Final Research Achievements

We conducted small RNA microarray for the sera of postpartum cardiomyopathy (PPCM) patients with preeclampsia (PE), or healthy controls. We identified miR-320a/b as disease-specific miRNAs. We searched the target genes for miR-320a/b. Then, we picked up EIF2aK3(PERK).　Next, we examined the phenotype of control mice and tissue-specific PERK homogenous knockout (HKO) mice during the perinatal period and performed transcriptome analysis and pathway analysis. Cardiac-specific PERK deletion revealed PPCM phenotype. In the hearts of HKO mice, unfolded protein response, EIF2 signaling, NRF2 signaling, prolactin signaling, β-adrenergic signaling, NFAT-induced immune response, and angiogenesis were downregulated, while necroptosis, fatty acid oxidation, glycolysis, and hypoxia signaling were upregulated.
These results demonstrate that miR-320a/b-mediated PERK suppression plays a key role in pathophysiology of PPCM. MiR-320a/b could serve as a biomarker and therapeutic target for PPCM with PE.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

近年、既知の周産期心筋症のバイオマーカーである切断プロラクチンが血中に発現していない症例、及び既存の周産期心筋症治療薬であるブロモクリプチン不応例が多数報告されている。本研究成果で同定したmiR-320a/bは、切断プロラクチンの有無にかかわらず、新規診断的バイオマーカー及び治療標的として有望であると考えられた。