ArticlePloS one2015
Inhibition of bone morphogenetic protein signal transduction prevents the medial vascular calcification associated with matrix Gla protein deficiency.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 74 citations in OpenAlex.
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- Rapamycin reduces mineral density and promotes beneficial vascular remodeling in a murine model of severe medial arterial calcification.American journal of physiology. Heart and circulatory physiology · 2025Article
- Rapamycin Reduces Mineral Density and Promotes Beneficial Vascular Remodeling in a Murine Model of Severe Medial Arterial Calcification.bioRxiv : the preprint server for biology · 2025Article
- Exosomes Derived from Dialysis Patients' Serum Enhance Endothelial-Mesenchymal Transition and Calcification in Endothelial Cells.Kidney360 · 2025Article
- Metabolites and metabolism in vascular calcification: links between adenosine signaling and the methionine cycle.American journal of physiology. Heart and circulatory physiology · 2024Review
- Blood vessel organoids generated by base editing and harboring single nucleotide variation in Notch3 effectively recapitulate CADASIL-related pathogenesis.Molecular neurobiology · 2024Article
- The Implications of Aging on Vascular Health.International journal of molecular sciences · 2024Review
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- New Therapeutics Targeting Arterial Media Calcification: Friend or Foe for Bone Mineralization?Metabolites · 2022Review
- The Role and Research Progress of Inhibitor of Differentiation 1 in Atherosclerosis.DNA and cell biology · 2022Review
- Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction.Arteriosclerosis, thrombosis, and vascular biology · 2022Observational
- Vascular Calcification: New Insights Into BMP Type I Receptor A.Frontiers in pharmacology · 2022Review
- Improving Right Ventricular Function by Increasing BMP Signaling with FK506.American journal of respiratory cell and molecular biology · 2021Article
- Non-Transferrin-Bound Iron in the Spotlight: Novel Mechanistic Insights into the Vasculotoxic and Atherosclerotic Effect of Iron.Antioxidants & redox signaling · 2021Review
- Modulation of EndMT by Hydrogen Sulfide in the Prevention of Cardiovascular Fibrosis.Antioxidants (Basel, Switzerland) · 2021Review
- Regulatory Role of Sex Hormones in Cardiovascular Calcification.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveMatrix Gla protein (MGP) is reported to inhibit bone morphogenetic protein (BMP) signal transduction. MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and mesenchymal transition of endothelial cells (EndMT). In this study, we investigated the contribution of BMP signal transduction to the medial calcification that develops in MGP-deficient mice. APPROACH AND
resultsMGP-deficient mice (MGP(-/-)) were treated with one of two BMP signaling inhibitors, LDN-193189 or ALK3-Fc, beginning one day after birth. Aortic calcification was assessed in 28-day-old mice by measuring the uptake of a fluorescent bisphosphonate probe and by staining tissue sections with Alizarin red. Aortic calcification was 80% less in MGP(-/-) mice treated with LDN-193189 or ALK3-Fc compared with vehicle-treated control animals (P<0.001 for both). LDN-193189-treated MGP(-/-) mice survived longer than vehicle-treated MGP(-/-) mice. Levels of phosphorylated Smad1/5 and Id1 mRNA (markers of BMP signaling) did not differ in the aortas from MGP(-/-) and wild-type mice. Markers of EndMT and osteogenesis were increased in MGP(-/-) aortas, an effect that was prevented by LDN-193189. Calcification of isolated VSMCs was also inhibited by LDN-193189.
conclusionsInhibition of BMP signaling leads to reduced vascular calcification and improved survival in MGP(-/-) mice. The EndMT and osteogenic transdifferentiation associated with MGP deficiency is dependent upon BMP signaling. These results suggest that BMP signal transduction has critical roles in the development of vascular calcification in MGP-deficient mice.
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