Related Experiment Video
Updated: Nov 8, 2025
Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage
Published on: July 3, 2014
Causal associations of serum matrix metalloproteinase-8 level with ischaemic stroke and ischaemic stroke subtypes: a
Yiming Jia1, Daoxia Guo2,3, Kaixin Zhang1
1Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China.
Background And Purpose:
Elevated serum matrix metalloproteinase-8 (MMP-8) concentrations are associated with high risk of vascular disease, but the causality remains unclear. A two-sample Mendelian randomization (MR) study was performed to examine the causal effect of serum MMP-8 concentrations on the risk of ischaemic stroke, ischaemic stroke subtypes and coronary artery disease.
Methods:
Ten independent single-nucleotide polymorphisms related to serum MMP-8 concentrations were identified as instrumental variables from a genome-wide association study of 6049 European subjects. Genetic association estimates for ischaemic stroke were obtained from the Multiancestry Genome-wide Association Study of Stroke consortium with 446,696 European individuals. The inverse-variance weighted method was applied to assess the causal associations of serum MMP-8 with ischaemic stroke and its subtypes in the main analysis.
Results:
No significant causal association was observed for MMP-8 levels with total ischaemic stroke, large artery stroke or cardioembolic stroke. Genetically determined 1 - unit higher log-transformed serum MMP-8 concentration was associated with an increased risk of small vessel stroke (odds ratio 1.25; 95% confidence interval 1.12-1.39; p < 0.001). In secondary analysis, a similar adverse impact was reported for MMP-8 on coronary artery disease (odds ratio 1.05; 95% confidence interval 1.01-1.10; p = 0.017). Sensitivity analyses further confirmed the relationship between serum MMP-8 level and small vessel stroke and coronary artery disease. Mendelian randomization Egger regression showed no evidence of pleiotropic bias.
Conclusions:
High serum MMP-8 concentrations were causally associated with increased risks of small vessel stroke and coronary artery disease. The mechanism underlying the effect of serum MMP-8 on the vascular system requires further investigation.
Insights
High serum matrix metalloproteinase-8 (MMP-8) levels are causally linked to increased risks of small vessel stroke and coronary artery disease. Further research is needed to understand MMP-8
Area of Science:
- Cardiovascular Genetics
- Biomarkers in Vascular Disease
- Stroke Etiology
Background:
- Elevated serum matrix metalloproteinase-8 (MMP-8) is linked to vascular disease risk, but causality is unproven.
- Matrix metalloproteinase-8 (MMP-8) is an enzyme involved in extracellular matrix degradation.
- Understanding MMP-8's role is crucial for cardiovascular disease prevention.
Purpose of the Study:
- To investigate the causal effect of serum MMP-8 concentrations on ischaemic stroke and coronary artery disease.
- To analyze the association between MMP-8 and specific ischaemic stroke subtypes.
- To employ Mendelian randomization to assess causality.
Main Methods:
- A two-sample Mendelian randomization study design was utilized.
- Instrumental variables were identified using 10 single-nucleotide polymorphisms associated with serum MMP-8.
- Genetic association data from large-scale genome-wide association studies were analyzed.
Main Results:
- Serum MMP-8 showed no significant causal association with total ischaemic stroke, large artery stroke, or cardioembolic stroke.
- A 1-unit increase in log-transformed serum MMP-8 was associated with a 25% increased risk of small vessel stroke (OR 1.25, p < 0.001).
- Serum MMP-8 was also associated with a 5% increased risk of coronary artery disease (OR 1.05, p = 0.017).
Conclusions:
- High serum MMP-8 concentrations are causally associated with increased risks of small vessel stroke and coronary artery disease.
- The findings suggest MMP-8 as a potential causal factor in specific vascular diseases.
- Further investigation into the mechanisms linking MMP-8 to vascular pathology is warranted.
