Vascular calcification: pathophysiology and risk factors

Abstract

Vascular calcification can occur in nearly all arterial beds and in both the medial and intimal layers. The initiating factors and clinical consequences depend on the underlying disease state and location of the calcification. The best studied manifestation is coronary artery calcification, in part because of the obvious clinical consequences, but also because of CT-based imaging modalities. In the general population, the presence of coronary artery calcification increases cardiovascular risk above that predicted by traditional Framingham risk factors, suggesting the presence of nontraditional risk factors. In patients with chronic kidney disease (CKD), coronary artery calcification is more prevalent and markedly more severe than in the general population. In these CKD patients, nontraditional risk factors such as oxidative stress, advanced glycation end products, and disordered mineral metabolism are also more prevalent and more severe and offer mechanistic insight into the pathogenesis of vascular calcification.

Figure 1

Mesenchymal stem cells can differentiate to adipocytes, osteoblasts, chondrocytes, and vascular smooth muscle cells. The latter cells can also de-differentiate or transform to chondrocyte/osteoblast like cells by upregulation of transcription factors such as RUNX-2 and MSX2. These cells then lay down collagen and non-collagenous proteins in the intima or media AND incorporate calcium and phosphorus into matrix vesicles to initiate mineralization and further grow the mineral into hydroxyapatite. The overall positive calcium and phosphorus balance of most dialysis patients feeds both the cellular transformation and the generation of matrix vesicles. Ultimately, whether an artery calcifies or not, depends on the strength of the army of inhibitors standing by in the circulation and in the arteries. Reprinted with permission from[1].