ArticleClinical science (London, England : 1979)2021
Acid sphingomyelinase promotes SGK1-dependent vascular calcification.
Article in Clinical science (London, England : 1979), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Role of Inositol Hexakisphosphate Kinases in Vascular Smooth Muscle Cell Calcification.International journal of molecular sciences · 2026Article
- Blocking Sphingosine 1-phosphate Metabolism With Fingolimod Prevents the Progression of Vascular Smooth Muscle Cells Calcification in Chronic Kidney Disease.Journal of cellular physiology · 2026Article
- Heterogeneity of common carotid artery and abdominal aorta: an angle of sphingolipid metabolism in vascular smooth muscle cells.Biomedical engineering online · 2025Article
- TGFβ signaling regulates the response of the skeleton to phosphate.bioRxiv : the preprint server for biology · 2025Article
- Sphingosine kinase 1 inhibition aggravates vascular smooth muscle cell calcification.Pflugers Archiv : European journal of physiology · 2025Article
- Fisetin ameliorates vascular smooth muscle cell calcification via DUSP1-dependent p38 MAPK inhibition.Aging · 2025Article
- Article
- Vitamin DScientific reports · 2024Article
- Sphingolipids and Atherosclerosis: The Dual Role of Ceramide and Sphingosine-1-Phosphate.Antioxidants (Basel, Switzerland) · 2023Review
- The therapeutic potential of sphingolipids for cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Periostin Augments Vascular Smooth Muscle Cell Calcification via β-Catenin Signaling.Biomolecules · 2022Article
- Acid Sphingomyelinase, a Lysosomal and Secretory Phospholipase C, Is Key for Cellular Phospholipid Catabolism.International journal of molecular sciences · 2021Review
- Regulatory role of mammalian target of rapamycin signaling in exosome secretion and osteogenic changes in smooth muscle cells lacking acid ceramidase gene.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In chronic kidney disease (CKD), hyperphosphatemia is a key factor promoting medial vascular calcification, a common complication associated with cardiovascular events and high mortality. Vascular calcification involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs), but the complex signaling events inducing pro-calcific pathways are incompletely understood. The present study investigated the role of acid sphingomyelinase (ASM)/ceramide as regulator of VSMC calcification. In vitro, both, bacterial sphingomyelinase and phosphate increased ceramide levels in VSMCs. Bacterial sphingomyelinase as well as ceramide supplementation stimulated osteo-/chondrogenic transdifferentiation during control and high phosphate conditions and augmented phosphate-induced calcification of VSMCs. Silencing of serum- and glucocorticoid-inducible kinase 1 (SGK1) blunted the pro-calcific effects of bacterial sphingomyelinase or ceramide. Asm deficiency blunted vascular calcification in a cholecalciferol-overload mouse model and ex vivo isolated-perfused arteries. In addition, Asm deficiency suppressed phosphate-induced osteo-/chondrogenic signaling and calcification of cultured VSMCs. Treatment with the functional ASM inhibitors amitriptyline or fendiline strongly blunted pro-calcific signaling pathways in vitro and in vivo. In conclusion, ASM/ceramide is a critical upstream regulator of vascular calcification, at least partly, through SGK1-dependent signaling. Thus, ASM inhibition by repurposing functional ASM inhibitors to reduce the progression of vascular calcification during CKD warrants further study.
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