| First Author | Osako MK | Year | 2013 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 33 |
| Issue | 6 | Pages | 1287-96 |
| PubMed ID | 23580147 | Mgi Jnum | J:218869 |
| Mgi Id | MGI:5618602 | Doi | 10.1161/ATVBAHA.112.301099 |
| Citation | Osako MK, et al. (2013) Cross-talk of receptor activator of nuclear factor-kappaB ligand signaling with renin-angiotensin system in vascular calcification. Arterioscler Thromb Vasc Biol 33(6):1287-96 |
| abstractText | OBJECTIVE: Vascular calcification is accelerated by hypertension and also contributes to hypertension; however, it is an enigma why hypertension and vascular calcification are a vicious spiral. The present study elucidates the cross-talk between renin-angiotensin II system and receptor activator of nuclear factor-kappaB ligand (RANKL) system in vascular calcification. APPROACH AND RESULTS: Angiotensin (Ang) II (10(-7) mol/L) significantly increased calcium deposition as assessed by Alizarin Red staining, associated with a significant increase in the expression of RANKL, RANK, and bone-related genes, such as cbfa1 and msx2, in human aortic vascular smooth muscle cells. Infusion of Ang II (100 ng/kg per minute) in ovariectomized ApoE(-/-) mice under high-fat diet significantly increased the expression of RANKL system and calcification in vivo, whereas administration of Ang II receptor blocker (olmesartan, 3 mg/kg per day) decreased the calcification and bone markers' expression. In addition, male OPG(-/-) mice showed a significant increase in vascular calcification followed by Ang II infusion as compared with wild type. Conversely, RANKL significantly increased Ang II type 1 receptor and angiotensin II-converting enzyme expression in vascular smooth muscle cells via extracellular signal-regulated protein kinase phosphorylation. CONCLUSIONS: The present study demonstrated that Ang II significantly induced vascular calcification in vitro and in vivo through RANKL activation. In addition, RANKL activated renin-angiotensin II system, especially angiotensin II-converting enzyme and Ang II type 1 receptor. Cross-talk between renin-angiotensin II system and RANKL system might work as a vicious cycle to promote vascular calcification in atherosclerosis. Further studies to inhibit renin-angiotensin II system and RANKL may provide new therapeutic options to prevent and regress vascular calcification. |
