ArticleThe Journal of biological chemistry2022
PALMD regulates aortic valve calcification via altered glycolysis and NF-κB-mediated inflammation.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Integrative Genome-wide Association Meta-analysis of Aortic Aneurysm and Dissection Identifies Five Novel Genes.Genomics, proteomics & bioinformatics · 2025Pooled it
- Pooled it
- Rare type I collagen variants in early-onset bicuspid aortic valve disease: Overlap with Ehlers-Danlos syndrome and osteogenesis imperfecta.HGG advances · 2026Article
- Inflammation via JAK-STAT/HIF-1α Drives Metabolic Changes in Pentose Phosphate Pathway and Glycolysis That Support Aortic Valve Cell Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Fuelling aortic stenosis: the integral role of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3-mediated glycolysis in Lp(a)-induced valve inflammation.European heart journal open · 2025Article
- Glycolysis hijacked: a novel pathogenic role of lipoprotein(a) in valve disease.European heart journal open · 2025Article
- Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway.Journal of advanced research · 2025Article
- Thrombospondin-1 Silencing Ameliorates Osteoblastic Differentiation of Aortic Valve Interstitial Cells via Inhibiting Nuclear Factor-Cardiovascular therapeutics · 2025Article
- Regulation of osteogenic differentiation in vascular smooth muscle cells under high-glucose condition.Frontiers in endocrinology · 2025Review
- In vivo proximity proteomics uncovers palmdelphin (PALMD) as a Z-disc-associated mitigator of isoproterenol-induced cardiac injury.Acta pharmacologica Sinica · 2024Article
- Integrated machine learning and Mendelian randomization reveal PALMD as a prognostic biomarker for nonspecific orbital inflammation.Scientific reports · 2024Article
- Transcriptomic and spatial dissection of human ex vivo right atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease.Cell reports. Medicine · 2024Article
- Review
- Insights into the Inherited Basis of Valvular Heart Disease.Current cardiology reports · 2024Review
- Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024Review
- PRMT3 methylates HIF-1α to enhance the vascular calcification induced by chronic kidney disease.Molecular medicine (Cambridge, Mass.) · 2024Article
- PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment.Renal failure · 2023Article
- Uncoupling protein 2 modulates polarization and metabolism of human primary macrophages via glycolysis and the NF‑κB pathway.Experimental and therapeutic medicine · 2023Article
- Palmdelphin Deficiency Evokes NF-κB Signaling in Valvular Endothelial Cells and Aggravates Aortic Valvular Remodeling.JACC. Basic to translational science · 2023Article
- Influence of Aortic Valve Stenosis and Wall Shear Stress on Platelets Function.Journal of clinical medicine · 2023Review
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent genome-wide association and transcriptome-wide association studies have identified an association between the PALMD locus, encoding palmdelphin, a protein involved in myoblast differentiation, and calcific aortic valve disease (CAVD). Nevertheless, the function and underlying mechanisms of PALMD in CAVD remain unclear. We herein investigated whether and how PALMD affects the pathogenesis of CAVD using clinical samples from CAVD patients and a human valve interstitial cell (hVIC) in vitro calcification model. We showed that PALMD was upregulated in calcified regions of human aortic valves and calcified hVICs. Furthermore, silencing of PALMD reduced hVIC in vitro calcification, osteogenic differentiation, and apoptosis, whereas overexpression of PALMD had the opposite effect. RNA-Seq of PALMD-depleted hVICs revealed that silencing of PALMD reduced glycolysis and nuclear factor-κB (NF-κB)-mediated inflammation in hVICs and attenuated tumor necrosis factor α-induced monocyte adhesion to hVICs. Having established the role of PALMD in hVIC glycolysis, we examined whether glycolysis itself could regulate hVIC osteogenic differentiation and inflammation. Intriguingly, the inhibition of PFKFB3-mediated glycolysis significantly attenuated osteogenic differentiation and inflammation of hVICs. However, silencing of PFKFB3 inhibited PALMD-induced hVIC inflammation, but not osteogenic differentiation. Finally, we showed that the overexpression of PALMD enhanced hVIC osteogenic differentiation and inflammation, as opposed to glycolysis, through the activation of NF-κB. The present study demonstrates that the genome-wide association- and transcriptome-wide association-identified CAVD risk gene PALMD may promote CAVD development through regulation of glycolysis and NF-κB-mediated inflammation. We propose that targeting PALMD-mediated glycolysis may represent a novel therapeutic strategy for treating CAVD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.