重症心不全患者の予後予測が可能に!?～心臓プロテオーム解析による心不全予後予測タンパク質の同定～

2025-11-26

2025-11-25 東京大学

東京大学らの研究グループは、重症心不全患者の心臓組織をプロテオーム解析し、左室補助人工心臓(LVAD)装着後に心機能が回復するかを事前予測できるタンパク質を同定した。心機能が回復する患者では、ミトコンドリア関連タンパク質(特にIDH2)が高値で、細胞外基質タンパク質(特にPOSTN)が低値であることが判明。LVAD装着時にIDH2とPOSTNを測定することで、回復の可否を予測できると確認された。また、LVAD装着後の心臓ではミトコンドリア代謝が低下し、解糖系が亢進する代謝シフトが生じることも明らかとなった。本成果は、重症心不全における治療選択や予後判定を可能にし、個別化医療(プレシジョン・メディシン)の発展に寄与することが期待される。

本研究の概要図(心臓プロテオーム解析により心不全予後予測タンパク質が同定)

<関連情報>

機械的負荷軽減後の心臓回復に関わるプロテオームシグネチャー
Proteomic Signatures Involved in Cardiac Recovery After Mechanical Unloading

Yukako Shintani-Domoto, MD, PhD, Koji L. Ode, PhD, Seitaro Nomura, MD, PhD, Yoshiki Nagashima, Osamu Kinoshita, MD, PhD, Manami Katoh, MD, PhD, Takanobu Yamada, MD, PhD, …, and Masashi Fukayama, MD, PhD
Circulation Published: 24 November 2025
DOI:https://doi.org/10.1161/CIRCULATIONAHA.124.073093

Heart failure is a leading cause of death worldwide, and patients with severe heart failure require left ventricular assist device (LVAD) support.¹ LVAD is usually implanted as a bridge to transplantation (BTT) or destination but can be removed if the patient’s cardiac function recovers. However, the molecular predictors for cardiac prognosis after LVAD implantation remain elusive.

We performed liquid chromatography–mass spectrometry on myocardial samples from heart transplant recipients, including 14 BTT cases and 10 bridge to recovery (BTR) cases, excluding patients with myocarditis. This study was approved by the institutional review board of the University of Tokyo (No. 10162, G10032). The data that support the findings of this study are available from the first authors upon reasonable request. LVAD implantation duration averaged 849 days (range, 68–1,405) in BTT and 202.8 days (range, 77–428) in BTR (Figure [A]). Myocardial tissues were processed, and formalin-fixed and paraffin-embedded specimens were analyzed. Samples from BTT were collected at both LVAD implantation (pre-LVAD) and heart transplantation (post-LVAD), whereas BTR samples were collected only at LVAD implantation. The samples were analyzed by data-dependent tandem mass spectrometry with a mass spectrometer (Q-Exactive Mass Spectrometer, Thermo Fisher Scientific). Mass spectrometry data were analyzed and quantified using Proteome Discoverer version 1.4 (Thermo Fisher Scientific) with the Swiss-Prot section of the UniProtKB human database (as of May 28, 2014). Only proteins that were consistently quantified in at least 11 of 14 BTT patients and 8 out of 10 BTR patients were included in the statistical analysis.