MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke

Area of Science:

• Cardiovascular Research
• Neuroscience
• Molecular Biology

Background:

• Cardiovascular diseases are significantly more prevalent in individuals with neurological deficits.
• MicroRNA-126 (miR-126) plays a crucial role in vascular health, influencing remodeling and fibrosis.
• Emerging evidence suggests miR-126's involvement in the pathogenesis of cardiovascular diseases and stroke.

Purpose of the Study:

• To investigate the hypothesis that reduced miR-126 expression following ischemic stroke contributes to cardiac dysfunction.
• To elucidate the specific role of endothelial cell-derived miR-126 in post-stroke cardiac health.

Main Methods:

• Utilized wild-type, endothelial cell-specific miR-126 knockout, and control mice subjected to distal middle cerebral artery occlusion (dMCAo) to model ischemic stroke.
• Assessed cardiac hemodynamics and function using transthoracic Doppler echocardiography.
• Quantified miR-126 expression, target gene and protein levels (VCAM-1, MCP-1), cardiac hypertrophy, fibrosis, inflammation, and oxidative stress at 28 days post-stroke.

Main Results:

• Ischemic stroke in wild-type mice led to decreased cardiac ejection fraction, increased myocyte hypertrophy, fibrosis, inflammation, and oxidative stress.
• Stroke significantly reduced serum and cardiac miR-126 levels while increasing expression of miR-126 target genes (VCAM-1, MCP-1).
• Mice lacking endothelial miR-126 exhibited exacerbated cardiac dysfunction, hypertrophy, fibrosis, and inflammation post-stroke compared to controls.

Conclusions:

• Ischemic stroke directly induces cardiac dysfunction.
• Decreased miR-126 expression, particularly from endothelial cells, is a key mechanism contributing to cardiac dysfunction after stroke.
• Restoring miR-126 levels may offer a therapeutic strategy for post-stroke cardiac complications.