ArticleCardiovascular research2017
Regulation of vascular smooth muscle cell calcification by syndecan-4/FGF-2/PKCα signalling and cross-talk with TGFβ.
Article in Cardiovascular research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Elastin calcification during the initial stage of vascular calcification in kl/kl mice is suppressed by the calcimimetic upacicalcet.Scientific reports · 2026Article
- FGF family in health and disease.Molecular biomedicine · 2026Review
- Age Differences in Aortic Stenosis.Reviews in cardiovascular medicine · 2025Review
- Calcification of the elastic component: the impact on the cardiovascular system.Frontiers in cardiovascular medicine · 2025Review
- Super-Enhancer-Driven Syndecan-4 Regulates Intercellular Communication in Hypoxic Pulmonary Hypertension.Journal of the American Heart Association · 2024Article
- Effects of Empagliflozin on Vascular and Skeletal Mineralization in Hyperlipidemic Mice.Vascular pharmacology · 2024Article
- Associations between pan-immune-inflammation value and abdominal aortic calcification: a cross-sectional study.Frontiers in immunology · 2024Article
- Vascular calcification: from the perspective of crosstalk.Molecular biomedicine · 2023Review
- The Pulmonary Endothelial Glycocalyx Modifications in Glypican 1 Knockout Mice Do Not Affect Lung Endothelial Function in Physiological Conditions.International journal of molecular sciences · 2023Article
- Myocardial fibrosis and calcification are attenuated by microRNA-129-5p targeting Asporin and Sox9 in cardiac fibroblasts.JCI insight · 2023Article
- A nonobstructive condition: Medial arterial calcification.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Two-faced Janus: the dual role of macrophages in atherosclerotic calcification.Cardiovascular research · 2022Review
- Distinct role of mitochondrial function and protein kinase C in intimal and medial calcificationFrontiers in cardiovascular medicine · 2022Article
- The two facets of receptor tyrosine kinase in cardiovascular calcification-can tyrosine kinase inhibitors benefit cardiovascular system?Frontiers in cardiovascular medicine · 2022Review
- Glypican 1 and syndecan 1 differently regulate noradrenergic hypertension development: Focus on IP3R and calcium.Pharmacological research · 2021Article
- Role of Glycosylation in Vascular Calcification.International journal of molecular sciences · 2021Review
- Multiple functions of autophagy in vascular calcification.Cell & bioscience · 2021Review
- Molecular mechanisms of osteogenesis and antibacterial activity of Cu-bearing Ti alloy in a bone defect model with infectionJournal of orthopaedic translation · 2021Article
- Dermatologic Adverse Events Associated with Selective Fibroblast Growth Factor Receptor Inhibitors: Overview, Prevention, and Management Guidelines.The oncologist · 2021Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
aimsVascular calcification is a major cause of morbidity and mortality. Fibroblast growth factor-2 (FGF-2) plays an instructive role in osteogenesis and bone development, but its role in vascular calcification was unknown. Therefore, we investigated the involvement of FGF-2 in vascular calcification and determined the mechanism by which it regulates this process. METHODS AND
resultsWe demonstrate that FGF-2 expression is increased in vascular smooth muscle cells (VSMCs) induced to deposit a mineralized matrix by incubation with β-glycerophosphate. FGF-2 is also localized to sites of calcification within human atherosclerotic plaques. The expression of syndecan-4, a heparan sulfate proteoglycan which regulates FGF-2 signalling, is also increased in mineralizing VSMCs and co-localizes with FGF-2 in human calcified atherosclerotic plaques. Exogenous FGF-2 inhibits VSMC mineralization, and this inhibition is reduced when syndecan-4 expression is knocked-down using siRNA. Biochemical inhibition of FGFR signalling using a pan FGFR inhibitor (BGJ398) or knocking-down syndecan-4 expression in VSMCs using siRNA increases VSMC mineralization. These increases are prevented by inhibiting transforming growth factor-β (TGFβ) signalling with SB431542, suggesting cross-talk between FGF-2 and TGFβ signalling is crucial for the regulation of VSMC mineralization. Syndecan-4 can also regulate FGF-2 signalling directly via protein kinase Cα (PKCα) activation. Biochemical inhibition of PKCα activity using Gö6976, or siRNA-mediated suppression of PKCα expression increases VSMC mineralization; this increase is also prevented with SB431542. Finally, the ability of FGF-2 to inhibit VSMC mineralization is reduced when PKCα expression is knocked-down.
conclusionThis is the first demonstration that syndecan-4 promotes FGF-2 signalling, and in turn, suppresses VSMC mineralization by down-regulating TGFβ signalling. Our discoveries that FGF-2 and syndecan-4 expression is increased in mineralizing VSMCs and that PKCα regulates FGF-2 and TGFβ signalling in VSMCs suggests that the syndecan-4/FGF-2/TGFβ signalling axis could represent a new therapeutic target for vascular calcification.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.