Heme-Mediated Activation of the Nrf2/HO-1 Axis Attenuates Calcification of Valve Interstitial Cells
نویسندگان
چکیده
Calcific aortic valve stenosis (CAVS) is a heart disease characterized by the progressive fibro-calcific remodeling of valves, an actively regulated process with involvement reactive oxygen species-mediated differentiation valvular interstitial cells (VICs) into osteoblast-like cells. Nuclear factor erythroid 2-related 2 (Nrf2) regulates expression variety antioxidant genes, and plays protective role in calcification. Heme oxygenase-1 (HO-1), Nrf2-target gene, upregulated human calcified valves. Therefore, we investigated effect Nrf2/HO-1 axis VIC We induced osteogenic VICs elevated phosphate calcium-containing medium (OM) presence heme. inhibited Ca deposition OM-induced increase alkaline phosphatase osteocalcin (OCN) expression. Nrf2 HO-1 VICs. lost its anti-calcification potential when blocked transcriptional activity or enzyme HO-1. The heme catabolism products bilirubin, carbon monoxide, iron, also ferritin OCN This study suggests that heme-mediated activation pathway inhibits calcification attributed to end HO-1-catalyzed degradation ferritin.
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OBJECTIVE Extensive remodeling of the valve ECM in calcific aortic valve sclerosis alters its mechanical properties, but little is known about the impact of matrix mechanics on the cells within the valve interstitium. In this study, the influence of matrix stiffness in modulating calcification by valve interstitial cells (VICs), and their differentiation to pathological phenotypes was assessed....
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ژورنال
عنوان ژورنال: Biomedicines
سال: 2021
ISSN: ['2227-9059']
DOI: https://doi.org/10.3390/biomedicines9040427