biostudies-literatureYao QNHLBI NIH HHS1410862https://www.ebi.ac.uk/biostudies/studies/S-EPMC11458440biostudies-literatureUnknown11<h4>Background</h4>Human Aortic valve interstitial cells (AVICs) from calcific aortic valve disease (CAVD)-affected valves exhibit elevated fibrocalcific activity although the underlying mechanism remains incompletely understood. This study aimed to identify endogenous factors that promote aortic valve fibrocalcification.<h4>Methods and results</h4>Proteomic analysis found increased cathepsin D levels in AVICs from CAVD-affected valves compared to AVICs from normal valves, and this finding was validated by immunoblotting. ELISA assay identified exacerbated release of cathepsin D by AVICs of diseased valves. Recombinant human cathepsin D upregulated the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), collagen I and collagen IV in human AVICs, resultingFrontiers in cardiovascular medicineCathepsin D elevates the fibrocalcific activity in human aortic valve cells through the ERK1/2-Sox9 pathway.PMC11458440R01 HL121776Zhai YAo LThe EFullerton DAYao QNedumaran BMeng XfalseCathepsin D elevates the fibrocalcific activity in human aortic valve cells through the ERK1/2-Sox9 pathway.<h4>Background</h4>Human Aortic valve interstitial cells (AVICs) from calcific aortic valve disease (CAVD)-affected valves exhibit elevated fibrocalcific activity although the underlying mechanism remains incompletely understood. This study aimed to identify endogenous factors that promote aortic valve fibrocalcification.<h4>Methods and results</h4>Proteomic analysis found increased cathepsin D levels in AVICs from CAVD-affected valves compared to AVICs from normal valves, and this finding was validated by immunoblotting. ELISA assay identified exacerbated release of cathepsin D by AVICs of diseased valves. Recombinant human cathepsin D upregulated the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), collagen I and collagen IV in human AVICs, resulting2024-01-01T00:00:00Z20242026-07-14T19:44:00.14Z2025-04-03T23:48:47.531ZS-EPMC114584403938062910.3389/fcvm.2024.1410862