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Matrix Metalloproteinase and Aortic Aneurysm: A Two-sample Mendelian Randomization Study.

Tao Qin1, Jiankai Zhong2, Pinglan Li1

  • 1Department of Ultrasound, Shunde Hospital, Southern Medical University, (The First People's Hospital of Shunde Foshan), Foshan, China.

Annals of Vascular Surgery
|April 12, 2024
PubMed
Summary

Matrix metalloproteinase-12 (MMP-12) is causally linked to reduced risks of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). Higher MMP-12 serum levels are associated with decreased TAA and AAA incidence, suggesting a protective role.

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Area of Science:

  • Genetics
  • Cardiovascular Science
  • Biochemistry

Background:

  • Matrix metalloproteinases (MMPs) are implicated in thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA).
  • Specific MMPs involved in aneurysm development remain unclear.
  • Mendelian randomization (MR) is a valuable tool for investigating causal relationships.

Purpose of the Study:

  • To investigate the causal relationship between specific matrix metalloproteinases (MMPs) and the risk of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA).
  • To identify potential therapeutic targets for aneurysm prevention and treatment.

Main Methods:

  • A two-sample Mendelian randomization (MR) analysis was conducted using Genome-Wide Association Studies (GWAS) data.
  • Eight MMPs (MMP-1, -2, -3, -8, -9, -10, -12, -13) and TAA/AAA data from the FinnGen consortium were analyzed.
  • The inverse variance weighted (IVW) method was the primary analytical approach, with assessments for heterogeneity and horizontal pleiotropy.

Main Results:

  • A significant inverse causal association was found between serum MMP-12 levels and both TAA and AAA.
  • Increased MMP-12 levels correlated with a reduced incidence of TAA (OR=0.897, P=0.005) and AAA (OR=0.835, P=0.001).
  • No significant heterogeneity or horizontal pleiotropy was detected in the MR analysis.

Conclusions:

  • Serum MMP-12 levels are causally associated with a reduced risk of TAA and AAA.
  • MMP-12 demonstrates a protective effect against the development of both thoracic and abdominal aortic aneurysms.
  • Targeting MMP-12 may represent a novel therapeutic strategy for aneurysm disease.