Soluble adhesion molecules and functional outcome after ischemic stroke: A Mendelian randomization study.

Area of Science:

• Cardiovascular Science
• Genetics
• Neurology

Background:

• Endothelial-derived adhesion molecules play a role in vascular inflammation.
• Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular-leukocyte adhesion molecule-1 (sVCAM-1), and soluble-endothelial-leukocyte adhesion molecule (sE-selectin) are key markers.
• Their association with functional outcomes after ischemic stroke requires elucidation.

Purpose of the Study:

• To investigate the causal relationship between genetically predicted circulating levels of sICAM-1, sVCAM-1, and sE-selectin and functional outcome following ischemic stroke.
• To determine if these adhesion molecules are potential predictors of post-stroke recovery.

Main Methods:

• Mendelian randomization analysis was utilized.
• Independent genetic variants (cis-acting) associated with soluble adhesion molecules served as instrumental variables.
• Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months post-stroke in a cohort of 6,021 individuals.

Main Results:

• Genetically elevated sICAM-1 levels were associated with a higher likelihood of poor functional outcome (mRS ≥ 3) after ischemic stroke (OR 1.28, 95% CI 1.05-1.56).
• Genetically elevated sE-selectin levels showed a significant association with poor post-stroke functional outcome (OR 2.69, 95% CI 1.23-5.86).
• No significant association was found between genetically elevated sVCAM-1 levels and post-stroke functional outcome (OR 1.36, 95% CI 0.39-4.66).

Conclusions:

• Higher genetically predicted levels of sICAM-1 and sE-selectin are associated with adverse functional outcomes after ischemic stroke.
• These findings suggest that ICAM-1 and E-selectin could be potential therapeutic targets to improve recovery following stroke.
• Further research is recommended to explore the therapeutic potential of targeting these adhesion molecules.