| First Author | Yao Y | Year | 2009 |
| Journal | Circ Res | Volume | 105 |
| Issue | 6 | Pages | 575-84 |
| PubMed ID | 19661459 | Mgi Jnum | J:169973 |
| Mgi Id | MGI:4943649 | Doi | 10.1161/CIRCRESAHA.109.202333 |
| Citation | Yao Y, et al. (2009) Heat shock protein 70 enhances vascular bone morphogenetic protein-4 signaling by binding matrix Gla protein. Circ Res 105(6):575-84 |
| abstractText | RATIONALE: Matrix Gla protein (MGP) is a calcification inhibitor, which binds and inhibits bone morphogenetic protein (BMP)-2 and -4. OBJECTIVE: The objective was to determine whether MGP also binds other proteins, which could interfere with its function. METHODS AND RESULTS: We transfected bovine aortic endothelial cells with N-terminally FLAG-tagged MGP and used immunoprecipitation and liquid chromatographic-tandem mass spectrometric analysis to identify MGP-binding proteins. Heat shock protein (HSP)70, a stress-induced protein expressed in atherosclerotic lesions and soluble in serum, was identified as a novel MGP-binding protein. The interaction between MGP and HSP70 was confirmed by coimmunoprecipitation and chemical crosslinking, and blocked the interaction between MGP and BMP-4. In endothelial cells, HSP70 enhanced BMP-4-induced proliferation and tube formation, and in calcifying vascular cells, HSP70 enhanced BMP-induced calcium deposition. In addition, HSP70 mediated the procalcific effect of interleukin-6 on calcifying vascular cells. In apolipoprotein E-null mice, a model for atherosclerosis, levels of BMP-4, HSP70, MGP, and interleukin-6 were elevated in the aortic wall. Levels of BMP-4, HSP70, and interleukin-6 were also elevated in serum, and anti-HSP70 antibodies diminished its procalcific effect on calcifying vascular cells. CONCLUSION: HSP70 binds MGP and enhances BMP activity, thereby functioning as a potential link between cellular stress, inflammation, and BMP signaling. |
