Key result
Palmatine inhibits aortic valve calcification by directly binding GAPDH and reducing its lactylation.
Its licence doesn't allow us to show a copy here.
Why the study?
Calcific aortic valve disease is a prevalent cardiovascular disorder lacking effective pharmacotherapy, motivating investigation of palmatine's therapeutic potential and molecular mechanisms.
Does palmatine inhibit osteogenic differentiation and calcification in preclinical models of calcific aortic valve disease?
Does palmatine inhibit osteogenic differentiation and calcification in preclinical models of calcific aortic valve disease?
Palmatine suppresses osteogenic differentiation and calcification by inhibiting GAPDH K263 lactylation, highlighting a potential novel pharmacological target for calcific aortic valve disease.
No immediate clinical implications; hypothesis-generating for targeting GAPDH lactylation in calcific aortic valve disease.
Calcific aortic valve disease (CAVD) is a prevalent cardiovascular disorder for which no effective pharmacotherapy has been approved. This study aims to investigate the therapeutic potential of palmatine (PAL) in CAVD and to elucidate the underlying molecular mechanism, with a focus on its role in metabolic-epigenetic crosstalk. The anti-calcification effect of PAL was evaluated in human aortic valve interstitial cells (hVICs) using qRT-PCR, Western blotting, and Alizarin Red S staining. Integrated multi-omics profiling (transcriptomics and metabolomics) together with lactylomics revealed that PAL primarily interferes with glycolytic metabolism and global lysine lactylation levels. The interaction between PAL and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was assessed via molecular docking and surface plasmon resonance (SPR). The functional significance of GAPDH K263 lactylation (K263lac) was investigated using site-specific mutagenesis. PAL treatment significantly inhibited osteogenic differentiation and calcification of hVICs. Mechanistically, PAL directly bound to GAPDH, selectively reducing its lactylation at the K263 residue. Mutating K263 to arginine (K263R) mimicked the effect of PAL, abrogating the PAL-mediated suppression of glycolysis, osteogenic gene expression, and calcium deposition. Immunofluorescence analysis further confirmed that PAL treatment markedly reduced cytoplasmic K263lac levels, and the K263R mutation completely abolished this modification. In vivo, PAL administration in a high-fat diet-fed ApoE
No takes yet. Share an insight, caveat, or question.
Du et al. (2026) studied Calcific aortic valve disease. Palmatine was evaluated on Osteogenic differentiation and calcification. Palmatine inhibited osteogenic differentiation and calcification of human aortic valve interstitial cells by directly binding to GAPDH and reducing its lactylation at K263.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: