Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian

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Updated: May 17, 2025

Quantitative Micro-CT Analysis of Aortopathy in a Mouse Model of β-aminopropionitrile-induced Aortic Aneurysm and Dissection
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Quantitative Micro-CT Analysis of Aortopathy in a Mouse Model of β-aminopropionitrile-induced Aortic Aneurysm and Dissection

Published on: July 16, 2018

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Lei Wang1,2, Yuzuo Lin3, Ziyan Lin3

  • 1Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, Fujian province, China.

Journal of Cardiothoracic Surgery
|April 4, 2025
PubMed
Abstract

Insights

Mitochondrial dysfunction is linked to aortic aneurysm (AA) and aortic dissection (AD). This study found specific mitochondrial proteins that may increase or decrease the risk of AA/AD, suggesting potential therapeutic targets.

Area of Science:

  • Cardiovascular Genetics
  • Mitochondrial Biology
  • Complex Disease Etiology

Background:

  • Mitochondrial dysfunction is implicated in the pathogenesis of aortic aneurysm (AA) and aortic dissection (AD).
  • Understanding the genetic underpinnings of mitochondrial involvement in AA/AD is crucial for risk assessment and prevention.

Purpose of the Study:

  • To investigate the potential causal associations between genetic variants of mitochondrial proteins and the risk of AA/AD.
  • To identify specific mitochondrial proteins that may serve as risk or protective factors for AA/AD.

Main Methods:

  • Utilized large-scale genome-wide association studies (GWAS) and FinnGen data for Mendelian randomization (MR) analysis.
  • Employed inverse-variance weighted (IVW) as the primary method, with sensitivity analyses (Cochran's Q, MR-Egger, MR-PRESSO, leave-one-out) to ensure result robustness.

Main Results:

  • Identified ISCU and NFU1 as potential risk factors for AA, while ribosomal protein L14 showed a protective effect.
  • Found ribosomal protein L33 and cytochrome C oxidase subunit 5B associated with increased AD risk, whereas ribosomal protein L52 and mitochondrial ubiquitin ligase activator of NFKB 1 demonstrated protective roles.

Conclusions:

  • Established potential genetic links between specific mitochondrial proteins and the risk of AA/AD.
  • Suggests that targeting identified mitochondrial proteins could offer novel strategies for preventing AA/AD.
Keywords:
Aortic aneurysmAortic dissectionMendelian randomizationMitochondria

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