| First Author | Jover E | Year | 2018 |
| Journal | FASEB J | Volume | 32 |
| Issue | 8 | Pages | 4459-4469 |
| PubMed ID | 29547702 | Mgi Jnum | J:276760 |
| Mgi Id | MGI:6307616 | Doi | 10.1096/fj.201700653R |
| Citation | Jover E, et al. (2018) Inhibition of enzymes involved in collagen cross-linking reduces vascular smooth muscle cell calcification. FASEB J 32(8):4459-4469 |
| abstractText | Vascular smooth muscle cells (VSMCs) transdifferentiate into osteoblast-like cells during vascular calcification, inducing active remodeling and calcification of the extracellular matrix (ECM). Intracellular and extracellular enzymes, such as lysyl hydroxylase 1 (PLOD1) and lysyl oxidase (LOX), contribute to ECM maturation and stabilization. We assessed the contribution of these enzymes to hyperphosphatemia-induced calcification. Human and murine VSMCs were differentiated into functional osteoblast-like cells by high-phosphate medium (HPM) conditioning. HPM promoted ECM calcification and up-regulated osteoblast markers associated with induction of LOX and PLOD1 expression and with an increase in ECM-insoluble collagen deposition. Murine VSMCs from transgenic mice overexpressing LOX (TgLOX) exhibited an increase in HPM-dependent calcification and osteoblast commitment compared with wild-type cells. Similarly, enhanced HPM-induced calcification was detected in aorta from TgLOX. Conversely, beta-aminopropionitrile (a LOX inhibitor) and LOX knockdown abrogated VSMC calcification and transdifferentiation. We found a significant positive association between LOX expression and vascular calcification in human atherosclerotic lesions. Likewise, 2,2'-dipyridil (a PLOD inhibitor) and PLOD1 knockdown impaired HPM-induced ECM mineralization and osteoblast commitment. Our findings identify LOX and PLOD as critical players in vascular calcification and highlight the importance of ECM remodeling in this process.-Jover, E., Silvente, A., Marin, F., Martinez-Gonzalez, J., Orriols, M., Martinez, C. M., Puche, C. M., Valdes, M., Rodriguez, C., Hernandez-Romero, D. Inhibition of enzymes involved in collagen cross-linking reduces vascular smooth muscle cell calcification. |
