ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2015
Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 188 citations in OpenAlex.
- Phase I studies of the safety, tolerability, pharmacokinetics, and pharmacodynamics of DS-1211, a tissue-nonspecific alkaline phosphatase inhibitor.Clinical and translational science · 2022Trial
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- Article
- Effects of comorbid chronic kidney disease on late-onset hypophosphatasia mice under treatment with asfotase alfa.JBMR plus · 2026Article
- A robust endothelial injury model inducing medial arterial calcification in C57BL/6J mice on a standard diet.Cardiovascular diagnosis and therapy · 2026Article
- ENPP1 inhibition as a therapeutic approach for later-onset hypophosphatasia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Hypophosphatasia-pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- Neuronal alkaline phosphatase promotes the spread of Tau-induced pathology, and its blockade prevents neurodegeneration and memory loss.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Intra-individual fluctuations in alkaline phosphatase predict mortality and CKD progression: insights from a large CKD cohort.Clinical kidney journal · 2026Article
- Article
- Inverse correlation between plasma pyrophosphate hydrolysis and early growth of abdominal aortic aneurysm: a pilot study.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Early-stage therapeutic efficacy of TNAP inhibition using a novel milder murine model of CKD-MBD.Experimental animals · 2026Article
- TNAP dephosphorylates phosphocholine and phosphoethanolamine and participates in triglyceride transport from the liver to the bloodstream.Communications biology · 2025Article
- Considerations on the Development of Therapeutics in Vascular Calcification.Journal of cardiovascular development and disease · 2025Review
- Association between albumin-to-alkaline phosphatase ratio and a 3-month unfavorable outcome in patients with acute ischemic stroke.Frontiers in nutrition · 2025Article
- Development and validation of a prediction model of hospital mortality for patients with cardiac arrest survived 24 hours after cardiopulmonary resuscitation.Frontiers in cardiovascular medicine · 2025Article
- Therapeutic approaches for the treatment of genetic and acquired cardiovascular calcification.Frontiers in cardiovascular medicine · 2025Review
- Novel Quantification Protocol for Cardiovascular Calcification Progression Using Longitudinal MicroPET/MicroCT Images.Journal of visualized experiments : JoVE · 2024Article
- Elevated glucose levels increase vascular calcification risk by disrupting extracellular pyrophosphate metabolism.Cardiovascular diabetology · 2024Article
- Zinc-alkaline phosphatase at sites of aortic calcification.Journal of molecular histology · 2024Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Medial vascular calcification (MVC) is a pathological phenomenon that causes vascular stiffening and can lead to heart failure; it is common to a variety of conditions, including aging, chronic kidney disease, diabetes, obesity, and a variety of rare genetic diseases. These conditions share the common feature of tissue-nonspecific alkaline phosphatase (TNAP) upregulation in the vasculature. To evaluate the role of TNAP in MVC, we developed a mouse model that overexpresses human TNAP in vascular smooth muscle cells in an X-linked manner. Hemizygous overexpressor male mice (Tagln-Cre(+/-) ; Hprt(ALPL) (/Y) or TNAP-OE) show extensive vascular calcification, high blood pressure, and cardiac hypertrophy, and have a median age of death of 44 days, whereas the cardiovascular phenotype is much less pronounced and life expectancy is longer in heterozygous (Tagln-Cre(+/-) ; Hprt(ALPL) (/-) ) female TNAP-OE mice. Gene expression analysis showed upregulation of osteoblast and chondrocyte markers and decreased expression of vascular smooth muscle markers in the aortas of TNAP-OE mice. Through medicinal chemistry efforts, we developed inhibitors of TNAP with drug-like pharmacokinetic characteristics. TNAP-OE mice were treated with the prototypical TNAP inhibitor SBI-425 or vehicle to evaluate the feasibility of TNAP inhibition in vivo. Treatment with this inhibitor significantly reduced aortic calcification and cardiac hypertrophy, and extended lifespan over vehicle-treated controls, in the absence of secondary effects on the skeleton. This study shows that TNAP in the vasculature contributes to the pathology of MVC and that it is a druggable target.
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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.