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Endostatin as a Mediator Between Endothelial Function and Cognitive Performance in Those at Risk for Vascular
Cameron Isaacs-Trepanier1, Mahwesh Saleem2, Nathan Herrmann2,3
1Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
Insights
Endostatin, an anti-angiogenic marker, mediates the link between endothelial function and cognitive performance in coronary artery disease patients. This finding highlights endostatin
Area of Science:
- Cardiovascular Research
- Neuroscience
- Angiogenesis Research
Background:
- Coronary artery disease (CAD) patients face higher risks of vascular cognitive impairment.
- Diminished endothelial function in CAD is linked to poorer cognitive performance.
- The precise mechanisms connecting endothelial function and cognition in CAD remain unclear, though angiogenesis is a potential mediator.
Purpose of the Study:
- To investigate whether angiogenesis markers mediate the relationship between endothelial function and cognitive performance in CAD patients.
- To explore the role of vascular endothelial growth factor (pro-angiogenic) and endostatin (anti-angiogenic) in this association.
Main Methods:
- Fifty CAD patients underwent assessment of endothelial function via peripheral arterial tonometry.
- Serum levels of vascular endothelial growth factor and endostatin were quantified.
- Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA); mediation analysis with bootstrapping was employed.
Main Results:
- Endostatin significantly mediated the association between endothelial function and cognitive performance, unlike vascular endothelial growth factor.
- This mediation effect persisted even when controlling for covariates like education, BMI, and diabetes.
- The mediation was also significant when using delayed recall scores from the MoCA.
Conclusions:
- Endostatin plays a mediating role in the relationship between endothelial function and cognitive performance among individuals with coronary artery disease.
- These findings suggest endostatin as a potential therapeutic target for mitigating cognitive decline in CAD.
Background:
Patients with coronary artery disease have an increased risk for developing vascular cognitive impairment. Endothelial function is often diminished and has been associated with lower cognitive performance in these patients. The link between endothelial function and cognition in coronary artery disease is not fully understood. Angiogenesis may play a role in mediating the association between endothelial function and cognition since angiogenic processes rely heavily on the endothelium.
Objective:
The aim of this study was to determine if markers of angiogenesis mediate the relationship between endothelial function and cognition in coronary artery disease patients.
Methods:
In 50 participants with coronary artery disease, endothelial function was assessed using peripheral arterial tonometry. Vascular endothelial growth factor (pro-angiogenic) and endostatin (anti-angiogenic) were measured in peripheral serum samples. Cognition was assessed using the Montreal Cognitive Assessment. A mediation analysis, using a bias corrected inferential bootstrapping method with 10,000 permutations, was used to determine if vascular endothelial growth factor or endostatin mediated an association between peripheral arterial tonometry measures and cognitive performance on the Montreal Cognitive Assessment.
Results:
Endostatin, but not vascular endothelial growth factor, mediated a relationship between endothelial function and cognitive performance when controlling for total years of education, body mass index, coronary artery bypass graft, stent, diabetes, and diuretic use. This analysis was also significant when delayed recall was substituted for the overall score on the Montreal Cognitive Assessment.
Conclusion:
These results suggest that endostatin mediates an association between endothelial function and cognitive performance in coronary artery disease.
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