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Updated: Aug 19, 2026
Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
Spatial heterogeneity of endothelial phenotypes correlates with side-specific vulnerability to calcification in
Craig A Simmons1, Gregory R Grant, Elisabetta Manduchi
1Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia PA 19104, USA. c.simmons@utoronto.ca
Insights
The aortic valve endothelium has distinct sides influencing calcification. Gene expression differences reveal why one side is more prone to calcific aortic valve sclerosis.
Area of Science:
- Cardiovascular Biology
- Vascular Endothelial Biology
- Molecular Biology
Background:
- Calcific aortic valve sclerosis (CAVS) involves inflammation and affects the aortic side of valve leaflets.
- Endothelial cell roles in vascular sclerosis are known, but valvular endothelial phenotypes and side-specific calcification susceptibility in CAVS remain unclear.
Purpose of the Study:
- To investigate differential gene expression in aortic valve endothelium.
- To understand side-specific endothelial phenotypes and their contribution to calcification susceptibility in CAVS.
Main Methods:
- Utilized RNA amplification and cDNA microarrays.
- Analyzed in situ gene expression differences between aortic and ventricular sides of normal adult pig aortic valves.
Main Results:
- Identified 584 differentially expressed genes between the two endothelial sides.
- Found distinct endothelial phenotypes with implications for valvular homeostasis and calcification.
- Observed reduced expression of cardiovascular calcification inhibitors on the aortic side, suggesting permissiveness to calcification.
- Noted enhanced antioxidative gene expression on the aortic side, potentially offering protection against inflammation.
Conclusions:
- Endothelium plays a role in regulating valvular calcification.
- Spatial heterogeneity in valvular endothelial phenotypes contributes to focal susceptibility for lesion development in CAVS.
Abstract:
Calcific aortic valve sclerosis involves inflammatory processes and occurs preferentially on the aortic side of endothelialized valve leaflets. Although the endothelium is recognized to play critical roles in focal vascular sclerosis, the contributions of valvular endothelial phenotypes to aortic valve sclerosis and side-specific susceptibility to calcification are poorly understood. Using RNA amplification and cDNA microarrays, we identified 584 genes as differentially expressed in situ by the endothelium on the aortic side versus ventricular side of normal adult pig aortic valves. These differential transcriptional profiles, representative of the steady state in vivo, identify globally distinct endothelial phenotypes on opposite sides of the aortic valve. Several over-represented biological classifications with putative relevance to endothelial regulation of valvular homeostasis and aortic-side vulnerability to calcification were identified among the differentially expressed genes. Of note, multiple inhibitors of cardiovascular calcification were significantly less expressed by endothelium on the disease-prone aortic side of the valve, suggesting side-specific permissiveness to calcification. However, coexisting putative protective mechanisms were also expressed. Specifically, enhanced antioxidative gene expression and the lack of differential expression of proinflammatory molecules on the aortic side may protect against inflammation and lesion initiation in the normal valve. These data implicate the endothelium in regulating valvular calcification and suggest that spatial heterogeneity of valvular endothelial phenotypes may contribute to the focal susceptibility for lesion development.
