curcumin and Heart-Valve-Diseases

Glutaraldehyde (GA) crosslinked bovine or porcine pericardium tissues exhibit high cell toxicity and calcification in the construction of bioprosthetic valves, which accelerate the failure of valve leaflets and motivate the exploration for alternatives. Polyphenols, including curcumin, procyanidin and quercetin, etc, have showed great calcification inhibition potential in crosslinking collagen and elastin scaffolds. Herein, we developed an innovative phenolic fixing technique by using curcumin as the crosslinking reagent for valvular materials. X-ray photoelectron spectroscopy and Fourier transform infrared spectrometry assessments confirmed the hydrogen bond between curcumin and acellular bovine pericardium. Importantly, the calcification inhibition capability of the curcumin-crosslinked bovine pericardium was proved by the dramatically reduced Ca

Topics: Animals; Bioprosthesis; Calcification, Physiologic; Cattle; Collagen; Cross-Linking Reagents; Curcumin; Elastin; Glutaral; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valves; Hemolysis; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Bonding; In Vitro Techniques; Materials Testing; Osteogenesis; Pericardium; Phenol; Photoelectron Spectroscopy; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Stress, Mechanical; Thermodynamics

The osteogenic differentiation of human aortic valve interstitial cells (hVICs) is the key cellular mechanism of calcified aortic valve disease (CAVD). This study aimed to explore how curcumin (CCM) inhibits the osteogenic differentiation of hVICs and elucidate the molecular mechanisms involved. In this study, CCM inhibited the osteogenic differentiation of hVICs under osteogenic medium (OM) conditions by reversing the OM-induced increase in calcified nodule formation and osteogenesis-specific markers (ALP and Runx2). RNA sequencing identified 475 common differentially expressed genes with Venn diagrams of the different groups. Kyoto Encyclopedia of Genes and Genomes enrichment revealed that the CCM inhibition of hVIC osteogenic differentiation was enriched in the NF-κB, PI3K-AKT, TNF, Jak-STAT, and MAPK signaling pathways. In addition, CCM suppressed the phosphorylation of ERK, IκBα, AKT, and interfered with the translocation of P65 into the cell nucleus in hVICs under OM culture conditions. In conclusion, CCM inhibited the osteogenic differentiation of hVICs via interfering with the activation of NF-κB/AKT/ERK signaling pathways. Our findings provide novel insights into a critical role for CCM in CAVD progression and shed new light on CCM-directed therapeutics for CAVD.

Topics: Aortic Valve; Aortic Valve Stenosis; Bicuspid Aortic Valve Disease; Calcinosis; Curcumin; Heart Defects, Congenital; Heart Valve Diseases; Humans; NF-kappa B; Proto-Oncogene Proteins c-akt