Figure 2.

Hypothetical mechanisms involved in the discussed treatments preventing vascular calcification. During hyperphosphatemia, phosphate complexes with calcium and forms secondary calciprotein particles, inducing osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs), which in turn generates a pro-calcific environment and subsequent active tissue mineralization. Oral bicarbonate treatment may impair intestinal phosphate reabsorption, ameliorating hyperhosphatemia. Renal carboanhydrase inhibition causes proton retention, which may reduce the formation of calcium-phosphate nanoparticles. Magnesium may similarly directly prevent calcium-phosphate complexation and stimulates the calcium sensing receptor in VSMCs, blunting osteo-chondrogenic transdifferentiation. This transdifferentiation is also directly stimulated by aldosterone, which may be blunted by spironolactone (spiro). Ammoniumchloride leads to lysosomal (lys) alkalinization which appears to dissipate the osteo-chondrogenic transdifferentiation of VSMCs. These mechanisms may provide the basis to develop a therapeutic approach to reduce the burden of vascular calcification.