Side-specific valvular endothelial-interstitial cell mechano-communication via cadherin-11.
Calcific aortic valve disease (CAVD) is a condition causing stiffening of the aortic valve, impeding cardiac function and resulting in significant morbidity worldwide. CAVD is thought to be driven by the persistent activation of the predominant cell type in the valve, aortic valve interstitial cells (AVICs), into myofibroblasts, resulting in subsequent calcification and stenosis of the valve. Although much of the research into CAVD focuses on AVICs, the aortic valve endothelial cells (AVECs) have been shown to regulate AVICs and maintain tissue homeostasis. Exposed to distinct flow patterns during the cardiac cycle, the AVECs lining either side of the valve demonstrate crucial differences which could contribute to the preferential formation of calcific nodules on the aorta-facing (fibrosa) side of the valve. Cadherin-11 (CDH11) is a cell-cell adhesion protein which has been previously associated with AVIC myofibroblast activation, nodule formation, and CAVD in mice. In this study, we investigated the role of CDH11 in AVECs and examined side-specific differences. The aorta-facing or fibrosa endothelial cells (fibAVECs) express higher levels of CDH11 than the ventricle-facing or ventricularis endothelial cells (venAVECs). This increase in expression corresponds with increased contraction of a free-floating collagen gel compared to venAVECs. Additionally, co-culture of fibAVECs with AVICs demonstrated decreased contraction compared to an AVIC + AVIC control, but increased contraction compared to the venAVECs co-culture. This aligns with the known preferential formation of calcific nodules on the fibrosa. These results together indicate a potential role for CDH11 expression by AVECs in regulating AVIC contraction and subsequent calcification.