Key result
Co-culturing aortic valve endothelial and interstitial cells increases induced calcification ~130% versus monocultures.
Why the study?
Aortic valve calcification is mediated by valve interstitial cells, but whether valve endothelial cells stimulate pro-osteogenic changes in them potentially via extracellular vesicles remained to be clarified.
Absolute Event Rate: 3% vs 1.3%
p-value: p=0.008
Valve endothelial cells from calcified aortic valves exhibit a pro-osteogenic phenotype and promote calcification of valve interstitial cells independently of extracellular vesicles.
In vitro data implicate VEC-derived EVs in VIC osteogenic changes; leaves open relevance to human aortic valve disease progression.
Aortic valve calcification is mediated by valve interstitial cells (VICs). We hypothesized that valve endothelial cells (VECs) stimulate pro-osteogenic changes in VICs, potentially via extracellular vesicles (EVs). We investigated VECs' pro-osteogenic effects on VICs, compared proteomes of healthy versus calcified VECs, and examined VECs-derived EVs effects on calcification. Human VECs and VICs were co-cultured in 2D and 3D (collagen gel) formats with osteogenic induction. Proteomic analysis compared VECs from healthy and calcified valves. Pro-osteogenic markers were assessed by qPCR, gel contractility was measured, and VECs-derived EVs were added to VICs cultures. In 2D co-cultures, induced calcification almost doubled versus VICs monocultures (p = 0.008). In 3D co-cultures, VECs from calcified valves induced strongest pro-osteogenic marker transcription in healthy VICs and reduced gel contraction. Proteomic analysis identified 3378 proteins with 27 and 8 proteins exclusive to healthy or calcified VECs, respectively. Nitric oxide synthase 3 and Hedgehog-interacting protein increased in calcified VECs (p = 0.005 and 0.002). VECs-derived EVs did not influence VICs calcification. VECs from calcified valves possess enhanced pro-osteogenic properties and promote VICs calcification independently of EVs. Pro-calcification EVs likely originate from other valve cell types.
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Evensen et al. (2026) studied Aortic valve calcification. Co-cultivation with valve endothelial cells (VECs) vs. Valve interstitial cells (VICs) monoculture was evaluated on Induced calcification measured by Alizarin red staining optical density (p=0.008). Co-cultivation of human aortic valve interstitial cells with valve endothelial cells almost doubled induced calcification compared to interstitial cell monocultures.
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