| First Author | Saddouk FZ | Year | 2016 |
| Journal | FASEB J | Volume | 30 |
| Issue | 3 | Pages | 1051-64 |
| PubMed ID | 26567004 | Mgi Jnum | J:230839 |
| Mgi Id | MGI:5766119 | Doi | 10.1096/fj.15-279158 |
| Citation | Saddouk FZ, et al. (2016) Ca2+/calmodulin-dependent protein kinase II-gamma (CaMKIIgamma) negatively regulates vascular smooth muscle cell proliferation and vascular remodeling. FASEB J 30(3):1051-64 |
| abstractText | Vascular smooth muscle (VSM) expresses calcium/calmodulin-dependent protein kinase II (CaMKII)-delta and -gamma isoforms. CaMKIIdelta promotes VSM proliferation and vascular remodeling. We tested CaMKIIgamma function in vascular remodeling after injury. CaMKIIgamma protein decreased 90% 14 d after balloon injury in rat carotid artery. Intraluminal transduction of adenovirus encoding CaMKIIgammaC rescued expression to 35% of uninjured controls, inhibited neointima formation (>70%), inhibited VSM proliferation (>60%), and increased expression of the cell-cycle inhibitor p21 (>2-fold). Comparable doses of CaMKIIdelta2 adenovirus had no effect. Similar dynamics in CaMKIIgamma mRNA and protein expression were observed in ligated mouse carotid arteries, correlating closely with expression of VSM differentiation markers. Targeted deletion of CaMKIIgamma in smooth muscle resulted in a 20-fold increase in neointimal area, with a 3-fold increase in the cell proliferation index, no change in apoptosis, and a 60% decrease in p21 expression. In cultured VSM, CaMKIIgamma overexpression induced p53 mRNA (1.7 fold) and protein (1.8-fold) expression; induced the p53 target gene p21 (3-fold); decreased VSM cell proliferation (>50%); and had no effect on expression of apoptosis markers. We conclude that regulated CaMKII isoform composition is an important determinant of the injury-induced vasculoproliferative response and that CaMKIIgamma and -delta isoforms have nonequivalent, opposing functions.-Saddouk, F. Z., Sun, L.-Y., Liu, Y. F., Jiang, M., Singer, D. V., Backs, J., Van Riper, D., Ginnan, R., Schwarz, J. J., Singer, H. A. Ca(2+)/calmodulin-dependent protein kinase II-gamma (CaMKIIgamma) negatively regulates vascular smooth muscle cell proliferation and vascular remodeling. |
