T-tubule remodeling and calcium handling dysfunction in fatal cardiac hypertrophy

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K10565
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58040:Forensics medicine-related
• Research Institution: Tokai University
• Principal Investigator: Kakimoto Yu 東海大学, 医学部, 准教授 (40734166)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 突然死 / 心肥大 / プロテオーム解析 / 異方性 / MYH7

Outline of Final Research Achievements

Cardiac tissues were sampled at autopsy. Sudden cardiac death (SCD) group consisted of ischemic heart failure and hypertensive heart failure. We performed histological examination, shotgun proteomic analysis, quantitative polymerase chain reaction analysis, and immunohistochemical analysis.
The proteomic profile revealed many sarcomere proteins were increased in SCD cases. Especially, the protein and mRNA levels of MYH7 and MYL3 were significantly increased in the SCD cases. Moreover, the level of MYH7 was significantly increased in the inner myocardial layer compared with the middle and outer layers in the heart.
This is the first report of cardiac proteomic analysis in SCD with hypertensive and ischemic heart failure. The stepwise upregulation of sarcomere proteins can increase the risk for SCD in acquired cardiac hypertrophy before the cardiac fibrosis prominently progresses.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

中高年では肥満や高血圧症に対して代償性に心肥大が生じることが多い。従来、心肥大が突然死のリスクとなることは知られていたが、心不全症状のない心肥大例において、突然死のリスクを正確に予測することは難しかった。
心肥大剖検例を対象とした本研究では、生理的心肥大群に比べて突然死群でMYH7とMYL3が増加していることが明らかとなり、心臓生検や血液検査においてこれらのタンパク質が突然死リスクマーカーとなる可能性が示された。将来的には、心肥大患者のなかでも突然死リスクの高い患者を識別することで、突然死の発症を予防することが期待できる。