| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 6000292 | Thrombosis Research | 2016 | 8 Pages |
â¢BMP-7 enhances all steps of monocyte extravasation.â¢BMP-7 activates the Akt-FAK signalling pathway in human monocytes.â¢Inhibitors of BMP signalling abrogate BMP-7â²s effects on monocyte motility.
BackgroundBone morphogenetic protein (BMP) 7 is abundant in atherosclerotic plaques and increases monocyte pro-coagulant activity by enhancing tissue factor (TF) expression. While several members of the BMP superfamily are able to serve as chemotactic agents for monocytes, the role of BMP-7 in regulation of monocyte motility is not known.AimsTo assess the effect of BMP-7 on adhesive and migratory properties of human monocytes.MethodsChemokinesis, adhesion, and transendothelial migration of BMP-7-treated THP-1 cells and human monocytes were analysed using live-cell imaging, orbital shear, and Boyden chamber assays. Surface presentation of β2 integrins and phosphorylation status of Akt & focal adhesion kinase (FAK) were studied by flow cytometry and Western blot.ResultsHigh levels of BMP-7 protein were detectable in intimal regions of atherosclerotic plaques; BMP-7 significantly enhanced THP-1 and monocyte chemokinetic properties in vitro (1.21 + 0.01 and 1.76 + 0.21 fold increase in crawling distance, respectively). Under orbital shear, adhesion of monocytic cells to microvascular endothelial cell (MVEC) monolayers was also significantly increased by BMP-7 (3.89 + 1.56 and 2.57 + 0.97 fold over vehicle). Moreover, BMP-7 accelerated transendothelial migration of THP-1 cells and monocytes towards MCP-1 (5.91 + 0.88 and 2.96 ± 0.65 fold increase, respectively). BMP-7 enhanced cell surface presentation of β2 integrins in the active conformation. Observed effects were determined to be Akt and FAK dependent, as shown by pharmacological inhibition.ConclusionBMP-7 directly upregulates adhesion and migration of human monocytic cells via activation of β2 integrins, Akt, and FAK. Our findings suggest that BMP-7 may serve as a novel contributor to atherogenesis.
