| First Author | Bai X | Year | 2010 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 30 |
| Issue | 12 | Pages | 2467-74 |
| PubMed ID | 20884873 | Mgi Jnum | J:183143 |
| Mgi Id | MGI:5317527 | Doi | 10.1161/ATVBAHA.110.215723 |
| Citation | Bai X, et al. (2010) Protein kinase C{delta} deficiency accelerates neointimal lesions of mouse injured artery involving delayed reendothelialization and vasohibin-1 accumulation. Arterioscler Thromb Vasc Biol 30(12):2467-74 |
| abstractText | OBJECTIVE: To use protein kinase C (PKC) delta-knockout mice to investigate the role of PKCdelta in lesion development and to understand the underlying mechanism of the vascular disease. METHODS AND RESULTS: PKCdelta functions as a signal transducer mediating several essential functions of cell proliferation and apoptosis. However, the effect of PKCdelta on neointimal formation in wire-injured vessels is unknown. Three weeks after wire injury of femoral arteries, neointimal lesions were significantly increased in PKCdelta(-/-) mice compared with PKCdelta(+/+) animals. Immunohistochemical staining revealed that total numbers of smooth muscle cells and macrophages in the lesions of PKCdelta(-/-) mice were markedly elevated without changing the ratio of these 2 cell types. To further elucidate the mechanisms of PKCdelta-mediated increase in the lesion, an in vivo endothelial migration model was established to evaluate endothelial wound healing after wire injury. Data showed that reendothelialization of the injured vessel was markedly delayed in PKCdelta(-/-) mice; this coincided with more severe intimal hyperplasia. Migration of endothelial cells cultivated from cardiac tissue was markedly reduced in the absence of PKCdelta, whereas no difference in proliferation or apoptosis was detected. Inhibition of PKCdelta activity or protein expression by small hairpin RNA (shRNA) in cultured endothelial cells confirmed the defective migratory phenotype. Interestingly, vasohibin-1, an antiangiogenesis protein, was elevated in endothelial cells derived from PKCdelta(-/-) mice, which was mainly because of delayed protein degradation mediated by PKCdelta. Downregulation of vasohibin-1 restored the migration rate of PKCdelta(-/-) endothelial cells to a similar level as PKCdelta(+/+) cells. CONCLUSIONS: PKCdelta deficiency enhances neointimal formation, which is associated with delayed reendothelialization and involves increased cellular vasohibin-1 accumulation. |
