| First Author | Li P | Year | 2014 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 34 |
| Issue | 9 | Pages | 2001-11 |
| PubMed ID | 25012128 | Mgi Jnum | J:227090 |
| Mgi Id | MGI:5699658 | Doi | 10.1161/ATVBAHA.113.303145 |
| Citation | Li P, et al. (2014) Cross talk between vascular smooth muscle cells and monocytes through interleukin-1beta/interleukin-18 signaling promotes vein graft thickening. Arterioscler Thromb Vasc Biol 34(9):2001-11 |
| abstractText | OBJECTIVE: Interleukin (IL)-1beta and IL-18 are key proinflammatory cytokines that play important roles in the pathophysiology of vein graft remodeling. However, the mechanism of IL-1beta/IL-18 production and its role in the development of graft remodeling remain unclear. APPROACH AND RESULTS: IL-1beta/IL-18 were rapidly expressed in venous interposition grafts. Vascular smooth muscle cell (VSMC) death and monocytic inflammasome activation occurred in grafted veins. Necrotic VSMCs induced the expression of IL-1beta, IL-18, and other inflammasome-associated proteins in monocytes, which was partially inhibited by their antagonist, recombinant IL-1ra-Fc-IL-18bp. Activated monocytes stimulated proliferation of VSMCs by activating cell growth-related signaling molecules (AKT, STAT3, ERK1/2, and mTOR [AKT/protein kinase B, signal transducer and activator of transcription 3, extracellular signal-regulated kinase 1/2, mammalian target of rapamycin]) and increasing production of platelet-derived growth factor-bb; these effects were suppressed by IL-1ra-Fc-IL-18bp. Activated monocytes also promoted migration of VSMCs, which was independent of IL-1beta/IL-18 signaling. Importantly, administration of IL-1ra-Fc-IL-18bp inhibited activation of cell growth-related signaling molecules, VSMC proliferation, and vein graft thickening in vivo. CONCLUSIONS: Our work identified an interaction among necrotic VSMCs, monocytes, and viable VSMCs through IL-1beta/IL-18 signaling, which might be exploited as a therapeutic target in vein graft remodeling. |
