Arterial Calcification in Chronic Kidney Disease: Key Roles for Calcium and Phosphate
By C. Shanahan, M. Crouthamel, A. Kapustin, C. Giachelli. Circulation Research, 2011
892 citations recorded by the source corpus.
Vascular calcification contributes to the high risk of cardiovascular mortality in chronic kidney disease (CKD) patients. Dysregulation of calcium (Ca) and phosphate (P) metabolism is common in CKD patients and drives vascular calcification. In this article, we review the physiological regulatory mechanisms for Ca and P homeostasis and the basis for their dysregulation in CKD. In addition, we highlight recent findings indicating that elevated Ca and P have direct effects on vascular smooth muscle cells (VSMCs) that promote vascular calcification, including stimulation of osteogenic/chondrogenic differentiation, vesicle release, apoptosis, loss of inhibitors, and extracellular matrix degradation. These studies suggest a major role for elevated P in promoting osteogenic/chondrogenic differentiation of VSMC, whereas elevated Ca has a predominant role in promoting VSMC apoptosis and vesicle release. Furthermore, the effects of elevated Ca and P are synergistic, providing a major stimulus for vascular calcification in CKD. Unraveling the complex regulatory pathways that mediate the effects of both Ca and P on VSMCs will ultimately provide novel targets and therapies to limit the destructive effects of vascular calcification in CKD patients.
Subfields: Nephrology, Nutrition and Dietetics
View Paper: https://www.semanticscholar.org/paper/131720fd0ba78896f6b03d63e6ec718d685d8bf8
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- A. Durham
- P. Lanzer
- M. Scatena
- Mei Y. Speer
- M. Boehm
- C. Giachelli
- C. Shanahan
- V. Sorribas
Citations in the corpus
- Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness (2018, background): “Calcium and phosphate added together act synergistically on VSMC in vitro to promote calcification, potentially though different mechanisms.(22) Cells in the presence of phosphate also show in increase in ALP activity, mimicking differentiating osteoblasts, and hypertrophic chondrocytes.”
- Medial vascular calcification revisited: review and perspectives. (2014, background): “During CKD (a major cause of VCm), a generalized, non-localized pro-inflammatory status is observed, with overexpression of TNFa, which could activate the osteochondrogenic programme in VSMCs.(12)”