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Pathogenesis of vascular calcification: experimental studies 

Pathogenesis of vascular calcification: experimental studies
Chapter:
Pathogenesis of vascular calcification: experimental studies
Author(s):

Rukshana C. Shroff

and Catherine M. Shanahan

DOI:
10.1093/med/9780199559176.003.017
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date: 23 February 2020

Experimental studies have elucidated many of the mechanisms that lead to calcification of the vessel wall in CKD. VSMC injury and death, loss of inhibitors and osteo/chondrocytic differentiation have been identified as key events in the calcification cascade. In addition experimental studies have identified many of the factors that contribute to VSMC damage and dysfunction in CKD and demonstrated how these factors impinge on one or more aspects of the calcification cascade. Importantly, dysregulated mineral metabolism appears to have a major impact on VSMC function and detailed studies aimed at further interrogating the molecular mechanisms, whereby dysregulated mineral metabolism impacts on VSMC function are now required. An issue that is now increasingly important to address is the relationship between vascular and bone health as potential therapies and interventions may impact on both these tissues. These studies cannot be performed in vitro and require a more complex physiological model system. Importantly, a number of animal models have now been developed that model CKD (Table 17.4). In addition, animal models of calcification specifically in the vasculature will be important in dissecting vessel and bone relationships. Also it should be remembered that vessel wall calcification occurs in the context of other disease states including atherosclerosis and diabetes and animal models superimposing these features on CKD have already proved informative and will provide important test systems for potential therapeutics.

Although we are still a long way from being able to inhibit the relentless progression of calcification in CKD, experimental studies have provided important insights and have identified targets for normalization as well as for therapeutic intervention and we await new experimental insights.

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