Abstract
Cardiovascular complications due to accelerated arterial stiffening and atherosclerosis are the leading cause of morbimortality in Western society. Both pathologies are frequently associated with vascular calcification. Pathologic calcification of cardiovascular structures, or vascular calcification, is associated with several diseases (for example, genetic diseases, diabetes, and chronic kidney disease) and is a common consequence of aging. Calcium phosphate deposition, mainly in the form of hydroxyapatite, is the hallmark of vascular calcification and can occur in the medial layer of arteries (medial calcification), in the atheroma plaque (intimal calcification), and cardiac valves (heart valve calcification). Although various mechanisms have been proposed for the pathogenesis of vascular calcification, our understanding of the pathogenesis of calcification is far from complete. However, in recent years, some risk factors have been identified, including high serum phosphorus concentration (hyperphosphatemia) and defective synthesis of pyrophosphate (pyrophosphate deficiency). The balance between phosphate and pyrophosphate, strictly controlled by several genes, plays a key role in vascular calcification. This review summarizes the current knowledge concerning phosphate and pyrophosphate homeostasis, focusing on the role of extracellular pyrophosphate metabolism in aortic smooth muscle cells and macrophages.
Highlights
Pathologic calcification of cardiovascular structures, or vascular calcification, is associated with several diseases, and is a common consequence of aging [1,2]
Different mechanisms regarding the pathogenesis of vascular calcification have been proposed [2], including (1) loss of inhibitions, (2) calcium and phosphorus homeostasis, (3) osteochondrogenic differentiation of vascular cells, (4) apoptosis, (5) circulating nucleation complexes/paracrine factors, and (6) matrix degradation
The currently known enzymes and transporters involved in extracellular pyrophosphate metabolism include members of the ecto-nucleotide pyrophosphatase/phosphodiesterase, tissue-nonspecific alkaline phosphatase, ecto-50 -nucleotidase, equilibrative nucleoside transporters, phosphate transporters (NaPi), progressive ankylosis proteins, and pump/channels that release ATP extracellularly, including the multi-drug resistance-associated protein 6 [21,64,65,66]
Summary
Pathologic calcification of cardiovascular structures, or vascular calcification, is associated with several diseases (for example, genetic diseases, diabetes, and chronic kidney disease), and is a common consequence of aging [1,2]. The deposition of phosphate-calcium crystals on the cardiovascular system, mainly in blood vessels, myocardium, and cardiac valves, is one of the most important factors determining patients’. In blood vessels, calcified deposits are found in distinct layers of the aortic wall and are associated with specific pathologies. Intimal calcification occurs in atherosclerotic lesions and is associated with vascular smooth muscle cells and macrophages [4]; whereas medial calcification (so-called “Monckeberg’s medial sclerosis”) occurs in the medial layer of the aortic wall and is associated with the collagen/elastin fibers and vascular smooth muscle cells [5,6].
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