Phosphate as a Pathogen of Arteriosclerosis and Aging.

Phosphate as a Pathogen of Arteriosclerosis and Aging. J Atheroscler Thromb. 2020 Oct 08;: Authors: Kuro-O M Abstract During the evolution of skeletons, terrestrial vertebrates acquired strong bones made of calcium-phosphate. By keeping the extracellular fluid in a supersaturated condition regarding calcium and phosphate ions, they created the bone when and where they wanted simply by providing a cue for precipitation. To secure this strategy, they acquired a novel endocrine system to strictly control the extracellular phosphate concentration. In response to phosphate intake, fibroblast growth factor-23 (FGF23) is secreted from the bone and acts on the kidney through binding to its receptor Klotho to increase urinary phosphate excretion, thereby maintaining phosphate homeostasis. The FGF23-Klotho endocrine system, when disrupted in mice, results in hyperphosphatemia and vascular calcification. Besides, mice lacking Klotho or FGF23 suffer from complex aging-like phenotypes, which are alleviated by placing them on a low-phosphate diet, indicating that phosphate is primarily responsible for the accelerated aging. Phosphate acquires the ability to induce cell damage and inflammation when precipitated with calcium. In the blood, calcium-phosphate crystals are adsorbed by serum protein fetuin-A and prevented from growing into large precipitates. Consequently, nanoparticles that comprised calcium-phosphate crystals and fetuin-A, termed calc...
Source: Journal of Atherosclerosis and Thrombosis - Category: Cardiology Tags: J Atheroscler Thromb Source Type: research