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Isolation and Primary Culture of Mouse Aortic Endothelial Cells
Published on: December 19, 2016
Coronary endothelium expresses a pathologic gene pattern compared to aortic endothelium: correlation of asynchronous
Michael B Dancu1, John M Tarbell
1Cardiovascular Dynamics and Biomolecular Transport Laboratory, Department of Biomedical Engineering, The City College of New York CUNY, New York, NY 10031, United States.
Insights
Asynchronous hemodynamics in coronary arteries correlate with pro-atherogenic gene expression. This study reveals how unique blood flow patterns in heart arteries may promote disease, unlike the aorta.
Area of Science:
- Cardiovascular Science
- Biomedical Engineering
- Molecular Biology
Background:
- Coronary arteries exhibit unique, asynchronous hemodynamics with wall shear stress (WSS) and circumferential strain (CS) out-of-phase.
- These hemodynamic features are distinct from the aorta and may predispose coronary arteries to disease.
Purpose of the Study:
- To investigate the in vivo correlation between asynchronous hemodynamics and endothelial cell (EC) pathology.
- To compare EC gene expression and nuclear morphology in coronary arteries versus the aorta.
Main Methods:
- Examined EC nuclear morphology using en face imaging in rabbit cLAD and aorta.
- Quantified EC gene expression (eNOS, ET-1) via real-time RT-PCR in different hemodynamic regions.
Main Results:
- EC nuclear morphology showed similarities between coronary arteries and the aorta.
- Coronary arteries displayed significantly reduced eNOS mRNA (>5-fold) and increased ET-1 mRNA (~2.5-fold) compared to aortic regions.
- Asynchronous hemodynamics in coronary arteries were associated with pro-atherogenic gene expression profiles.
Conclusions:
- Asynchronous hemodynamics in coronary arteries are linked to pro-atherogenic EC gene expression.
- Hemodynamic forces inherent to circulation play a role in inducing these gene expression patterns.
- Endothelial cell nuclear morphology did not differ between regions, suggesting gene expression is a primary indicator of hemodynamic influence.
Abstract:
Coronary arteries are the most disease prone arteries in the circulation and are characterized by unique hemodynamic features, wherein wall shear stress (WSS) induced by blood flow and circumferential strain (CS) driven by pressure are highly out-of-phase temporally (asynchronous hemodynamics). To investigate whether there is a correlation between asynchronous hemodynamics and pathology in vivo, we examined endothelial cell (EC) gene expression and nuclear morphology in two distinct hemodynamic regions of male New Zealand rabbits: coronary arteries (left anterior descending artery cLAD), and aorta (aortic arch inner curvature, outer curvature, and straight descending aorta). En face imaging showed strong similarities in EC nuclear length:width ratio and angle of orientation in the cLAD and aorta. Real-time RT-PCR, however, showed that coronary arteries had significantly reduced (>5-fold) eNOS mRNA levels compared to all aortic regions, while ET-1 showed an opposite trend ( approximately 2.5-fold). Coronary arteries with characteristic asynchronous hemodynamics displayed pro-atherogenic eNOS and ET-1 gene expression profiles while the EC nuclei morphology did not differ from non-atherogenic regions in the aorta. This study demonstrates a correlation between asynchronous hemodynamics and pro-atherogenic gene expression patterns in vivo that is induced by hemodynamics inherent to the circulation.
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