ArticleJournal of the American Heart Association2015
Transgenic Overexpression of Tissue-Nonspecific Alkaline Phosphatase (TNAP) in Vascular Endothelium Results in Generalized Arterial Calcification.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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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.
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Who cites it
56 citing papers in PubMed, 89 citations in OpenAlex.
- Article
- 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
- Decoding vascular calcification: mechanistic insights and translational strategies.Cellular and molecular life sciences : CMLS · 2026Review
- Atherosclerosis: A Pathologist's Perspective.Journal of cardiovascular development and disease · 2026Review
- Early-stage therapeutic efficacy of TNAP inhibition using a novel milder murine model of CKD-MBD.Experimental animals · 2026Article
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- Phosphate in Physiological and Pathological Mineralization: Important yet Often Unheeded.MedComm · 2025Review
- Considerations on the Development of Therapeutics in Vascular Calcification.Journal of cardiovascular development and disease · 2025Review
- Atherosclerosis: A Comprehensive Review of Molecular Factors and Mechanisms.International journal of molecular sciences · 2025Review
- A preliminary study on calcifying nanoparticles in dental plaque: Isolation, characterization, and potential mineralization mechanism.Clinical and experimental dental research · 2024Article
- Weighing the Evidence for the Roles of Plasma Versus Local Pyrophosphate in Ectopic Calcification Disorders.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Implications of Senescent Cell Burden and NRF2 Pathway in Uremic Calcification: A Translational Study.Cells · 2023Article
- A Proteomic Screen to Unravel the Molecular Pathways Associated with Warfarin-Induced or TNAP-Inhibited Arterial Calcification in Rats.International journal of molecular sciences · 2023Article
- Gene Therapy Using Recombinant AAV Type 8 Vector Encoding TNAP-DJBMR plus · 2023Article
- Serum Homocysteine and Vascular Calcification: Advances in Mechanisms, Related Diseases, and Nutrition.Korean journal of family medicine · 2022Article
- A new perspective on the function of Tissue Non-Specific Alkaline Phosphatase: from bone mineralization to intra-cellular lipid accumulation.Molecular and cellular biochemistry · 2022Review
- Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation.Biomedicines · 2022Article
- Vascular Calcification in Chronic Kidney Disease: An Update and Perspective.Aging and disease · 2022Article
- Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease.Nutrients · 2022Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundEctopic vascular calcification is a common condition associated with aging, atherosclerosis, diabetes, and/or chronic kidney disease. Smooth muscle cells are the best characterized source of osteogenic progenitors in the vasculature; however, recent studies suggest that cells of endothelial origin can also promote calcification. To test this, we sought to increase the osteogenic potential of endothelial cells by overexpressing tissue-nonspecific alkaline phosphatase (TNAP), a key enzyme that regulates biomineralization, and to determine the pathophysiological effect of endothelial TNAP on vascular calcification and cardiovascular function. METHODS AND
resultsWe demonstrated previously that mice transgenic for ALPL (gene encoding human TNAP) develop severe arterial medial calcification and reduced viability when TNAP is overexpressed in smooth muscle cells. In this study, we expressed the ALPL transgene in endothelial cells following endothelial-specific Tie2-Cre recombination. Mice with endothelial TNAP overexpression survived well into adulthood and displayed generalized arterial calcification. Genes associated with osteochondrogenesis (Runx2, Bglap, Spp1, Opg, and Col2a1) were upregulated in the aortas of endothelial TNAP animals compared with controls. Lesions in coronary arteries of endothelial TNAP mice showed immunoreactivity to Runx2, osteocalcin, osteopontin, and collagen II as well as increased deposition of sialoproteins revealed by lectin staining. By 23 weeks of age, endothelial TNAP mice developed elevated blood pressure and compensatory left ventricular hypertrophy with preserved ejection fraction.
conclusionsThis study presented a novel genetic model demonstrating the osteogenic potential of TNAP-positive endothelial cells in promoting pathophysiological vascular calcification.
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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 Socratic graph.