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Ectopic calcification is characterized by inappropriate deposition of calcium mineral in nonskeletal connective tissues and can cause significant morbidity and mortality, particularly when it affects the cardiovascular system. Identification of the metabolic and genetic determinants of ectopic calcification could help distinguish individuals at the greatest risk of developing these pathological calcifications and could guide development of medical interventions. Inorganic pyrophosphate (PP ) has long been recognized as the most potent endogenous inhibitor of biomineralization. It has been intensively studied as both a marker and a potential therapeutic for ectopic calcification. Decreased extracellular concentrations of PP have been proposed to be a unifying pathophysiological mechanism for disorders of ectopic calcification, both genetic and acquired. However, are reduced plasma concentrations of PP a reliable predictor of ectopic calcification? This perspective article evaluates the literature in favor and against a pathophysiological role of plasma versus tissue PP dysregulation as a determinant of, and as a biomarker for, ectopic calcification. © 2023 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4791 | DOI Listing |
Am J Prev Cardiol
September 2025
Tsimane Health and Life History Project, San Borja, Bolivia.
Background: Greater deposits of epicardial adipose tissue are associated with atrial fibrillation and coronary disease, but have not been studied in subsistence populations.
Methods: We performed CT imaging to measure coronary artery and thoracic aortic calcium (CAC, TAC), epicardial fat thickness (EFT), liver density, and left atrial (LA) anteroposterior diameter and, using a deep learning-enabled software program, epicardial and thoracic fat volume (EFV, TFV), in two remote Amerindian subsistence populations with minimal coronary artery calcification and virtually no atrial fibrillation. We compared 893 adult Tsimane (mean age 58.
Exp Anim
September 2025
Daiichi Sankyo Co., Ltd.
Chronic kidney disease (CKD) is a complicated systemic disease displaying various pathophysiological symptoms including mineral bone disorder (CKD-MBD). Ideally, early intervention for CKD-MBD would be desirable, however, there is not enough evidence regarding treatment of CKD-MBD, especially in its early stages, due to its multifactorial pathophysiology and the difficulty in generating adequate animal models. In this study, we evaluated the efficacy of a tissue nonspecific alkaline phosphatase (TNAP) inhibitor, SBI-425 in a CKD-MBD animal model, produced by a combination of nephrectomy and high inorganic phosphate (P) diet.
View Article and Find Full Text PDFBiochem Biophys Rep
September 2025
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510100, China.
Pseudoxanthoma elasticum (PXE), caused by pathogenic variants in , is characterized by pathological ectopic calcification with poorly understood mechanisms and no effective therapies. To address this, we developed the first zebrafish model of human PXE by introducing the pathogenic point mutation ( , F2 generation) using the highly efficient zhyA3A-CBE5 cytosine base editor. Three mutant types (Type1-Type3, T1-T3) stratified by calcification severity, exhibited reduced levels of the calcification inhibitors vitamin K1 (VK1) and carboxylated matrix Gla protein (cMGP), which were inversely correlated with the severity of calcification.
View Article and Find Full Text PDFMol Brain
August 2025
Laboratory of Medical Therapeutics and Molecular Therapeutics, Department Biomedical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu City, 501-1196, Gifu, Japan.
Primary brain calcification (PBC) is a neurodegenerative disease that causes bilateral ectopic calcification in the brain. In this study, using newly generated Slc20a2 knockout (Slc20a2) mice, we establish an in vivo model for PBC. In contrast to heterozygous Slc20a2 mice (9/9 animals) showing no obvious abnormalities, the homozygous Slc20a2 mice exhibited severe calcification at 11 months of age (5/5 animals).
View Article and Find Full Text PDFJ Surg Case Rep
August 2025
Department of Thoracic Surgery at Jersey Shore University Medical Center (JSUMC), 1945 Route 33, Neptune, NJ 07753, United States.
Ectopic pancreas (EP) is a rare congenital anomaly defined as pancreatic tissue lacking anatomical or vascular continuity with the pancreas. Although it occurs in 0.25%-2% of the population, mediastinal EP is exceedingly rare, with fewer than 30 reported cases.
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