title: Vascular Calcification in Uremia: New-Age Concepts about an Old-Age Problem.
abstract: A hallmark of aging, and major contributor to the increased prevalence of cardiovascular disease in patients with chronic kidney disease (CKD), is the progressive structural and functional deterioration of the arteries and concomitant accrual of mineral. Vascular calcification (VC) was long viewed as a degenerative age-related pathology that resulted from the passive deposition of mineral in the extracellular matrix; however, since the discovery of "bone-related" protein expression in calcified atherosclerotic plaques over 20 years ago, a plethora of studies have evoked the now widely accepted view that VC is a highly regulated and principally cell-mediated phenomenon that recapitulates many features of physiologic ossification. Central to this theory are changes in vascular smooth muscle cell (VSMC) phenotype and viability, thought to be driven by chronic exposure to a number of dystrophic stimuli characteristics of the uremic state. Here, dedifferentiated synthetic VSMCs are seen to spawn calcifying matrix vesicles that actively seed mineralization of the arterial matrix. This review provides an overview of the major epidemiological, histological, and molecular aspects of VC in the context of CKD, and a counterpoint to the prevailing paradigm that emphasizes the primacy of VSMC-mediated mechanisms. Particular focus is given to the import of protein and small molecule inhibitors in regulating physiologic and pathological mineralization and the emerging role of mineral nanoparticles and their interplay with proinflammatory processes.
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Parkville, VIC, 3050, Australia. edward.smith@mh.org.au.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Smith
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008903:Minerals / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles; D010012:Osteogenesis; D014511:Uremia / Q000209:etiology* / Q000473:pathology*; D061205:Vascular Calcification / Q000209:etiology* / Q000473:pathology*
chemical_list: D008903:Minerals
keywords: Aging; Chronic kidney disease; Inflammation; Mineral nanoparticles; Osteochondrocytic transdifferentiation; Vascular calcification