Heat shock protein 70 in the prevention of vascular calcification in renal failure

Abstract

Vascular calcification (VC) is highly correlated with cardiovascular mortality in renal failure. Osteo/chondrocytic transformation of human aortic smooth muscle cells (HA‐SMCs) is important in the initiation and progression of VC. In vitro and in vivo studies have shown this process can be driven under hyperphosphatemic and hypercalcemic conditions seen in renal failure. Several transcription factors, including Cbfa1/Runx2 is essential for induction of osteo/chondrocytic transformation.We previously demonstrated that HSP70 prevents vascular permeability changes in certain acute inflammatory processes. Studies have shown significantly higher circulating HSP70 levels in individuals with no evidence of coronary artery disease (CAD), while lower levels in pre‐dialysis patients, and even lower levels in hemodialysis (HD) patients were found.Our results have shown for the first time that heat‐shock treatment induced expression of HSP70 and markedly reduced the extent of calcification in HA‐SMCs, in vitro. Cbfa1 was upregulated in calcified HA‐SMCs, while heat‐shock treatment down‐regulates its expression. Furthermore, HSP70 expression was found to be lower in arteries from renal failure patients compared to healthy controls, ex vivo. In conclusion, HSP70 reduces the development of calcification through the inhibition of smooth muscle cell transformation.