Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease

Area of Science:

• Cardiovascular Biology
• Vascular Biology
• Tissue Engineering

Background:

• Calcific aortic valve disease (CAVD) involves pathological changes in aortic valve interstitial cells (VICs).
• The role of VICs in aortic valve vascularization, particularly angiogenesis, remains incompletely understood.

Purpose of the Study:

• To investigate the angiogenic capacity of human VICs isolated from patients with CAVD.
• To determine if VICs can differentiate into vascular lineages and influence endothelial cells.

Main Methods:

• VICs were isolated from human aortic valves with CAVD (pathological VICs, VICp) and normal valves.
• VICs were assessed for differentiation potential into endothelial and perivascular cells in vitro and in vivo.
• Paracrine effects of VICs on human endothelial colony-forming cells (ECCs) were evaluated using conditioned media and ELISA.
• Vascular endothelial growth factor-A (VEGF-A) involvement was confirmed using blocking antibodies and siRNA.

Main Results:

• Pathological VICs (VICp) exhibited a mesenchymal phenotype and multipotent differentiation capacity.
• VICp cocultured with ECCs formed microvessels, differentiating into perivascular cells.
• VICp-conditioned media significantly enhanced ECC proliferation, migration, and sprouting compared to control VICs.
• VICp-conditioned media showed higher levels of VEGF-A, and blocking VEGF-A inhibited the pro-angiogenic effects.

Conclusions:

• Human VICs from CAVD patients possess angiogenic potential.
• VICp can differentiate into perivascular cells and promote valve vascularization via VEGF-A secretion.
• Targeting VIC perivascular differentiation and VEGF-A may offer therapeutic strategies for CAVD progression.