Vascular calcification: lessons from scientific models.
Patients with chronic kidney disease have increased cardiovascular mortality from a combination of increased atherosclerotic disease, left ventricular hypertrophy and increased prevalence of vascular calcification (VC). Previously VC was thought to be a passive process which involved the deposition of calcium and phosphate into the vessel wall. However, recent studies have shown that VC is a highly regulated, cell-mediated process similar to bone formation, in that it is associated with expression of bone-related proteins, such as type I collagen and alkaline phosphatase. Animal and in vitro models of VC have shown that a multitude of factors including phosphate, matrix gla protein (MGP) and fetuin are involved in regulating VC. Certain factors induce calcification whereas others inhibit the process. Despite these insights, it is still not fully known how VC is regulated and a treatment for VC remains elusive. Ongoing research will hopefully elucidate these mechanisms and thereby produce targets for future therapeutic intervention. This review will highlight some of the scientific models of VC and how they have increased the understanding of this complex process.
Sinha
Smeeta
S
Salford Royal Foundation Trust Hospital, Salford M6 8HD, UK.
Eddington
Helen
H
Kalra
Philip A
PA
D000469:Alkaline Phosphatase / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology; D002114:Calcinosis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D002135:Calcium-Binding Proteins / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality; D024042:Collagen Type I / Q000502:physiology; D011756:Diphosphates; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D007249:Inflammation; D007676:Kidney Failure, Chronic / Q000150:complications*; D051379:Mice; D053495:Osteopontin / Q000502:physiology; D010758:Phosphorus / Q000502:physiology; D015995:Prevalence; D012307:Risk Factors; D014652:Vascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D014807:Vitamin D / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use; D000509:alpha-Fetoproteins / Q000502:physiology; D000097568:Matrix Gla Protein
D000469:Alkaline Phosphatase; D002135:Calcium-Binding Proteins; D024042:Collagen Type I; D011756:Diphosphates; D016326:Extracellular Matrix Proteins; D053495:Osteopontin; D010758:Phosphorus; D014807:Vitamin D; D014815:Vitamins; D000509:alpha-Fetoproteins; D000097568:Matrix Gla Protein