| First Author | Cheng C | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 5 | Pages | 1289-98 |
| PubMed ID | 22426130 | Mgi Jnum | J:196924 |
| Mgi Id | MGI:5490201 | Doi | 10.1161/ATVBAHA.112.245530 |
| Citation | Cheng C, et al. (2012) PDGF-induced migration of vascular smooth muscle cells is inhibited by heme oxygenase-1 via VEGFR2 upregulation and subsequent assembly of inactive VEGFR2/PDGFRbeta heterodimers. Arterioscler Thromb Vasc Biol 32(5):1289-98 |
| abstractText | OBJECTIVE: In cardiovascular regulation, heme oxygenase-1 (HO-1) activity has been shown to inhibit vascular smooth muscle cell (VSMC) proliferation by promoting cell cycle arrest at the G1/S phase. However, the effect of HO-1 on VSMC migration remains unclear. We aim to elucidate the mechanism by which HO-1 regulates PDGFBB-induced VSMC migration. METHODS AND RESULTS: Transduction of HO-1 cDNA adenoviral vector severely impeded human VSMC migration in a scratch, transmembrane, and directional migration assay in response to PDGFBB stimulation. Similarly, HO-1 overexpression in the remodeling process during murine retinal vasculature development attenuated VSMC coverage over the major arterial branches as compared with sham vector-transduced eyes. HO-1 expression in VSMCs significantly upregulated VEGFA and VEGFR2 expression, which subsequently promoted the formation of inactive PDGFRbeta/VEGFR2 complexes. This compromised PDGFRbeta phosphorylation and impeded the downstream cascade of FAK-p38 signaling. siRNA-mediated silencing of VEGFA or VEGFR2 could reverse the inhibitory effect of HO-1 on VSMC migration. CONCLUSIONS: These findings identify a potent antimigratory function of HO-1 in VSMCs, a mechanism that involves VEGFA and VEGFR2 upregulation, followed by assembly of inactive VEGFR2/PDGFRbeta complexes that attenuates effective PDGFRbeta signaling. |
