Details

Autor(en) / Beteiligte

• Li, Ping
• Li, Yu-lin
• Li, Zhen-ya
• Wu, Yi-na
• Zhang, Cong-cong
• A, Xi
• Wang, Chun-xiao
• Shi, Hong-tao
• Hui, Mi-zhou
• Xie, Bo
• Ahmed, Mohammed
• Du, Jie

Titel

Cross talk between vascular smooth muscle cells and monocytes through interleukin-1β/interleukin-18 signaling promotes vein graft thickening

Ist Teil von

• Arteriosclerosis, thrombosis, and vascular biology, 2014-09, Vol.34 (9), p.2001-2011

Ort / Verlag

United States

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Interleukin (IL)-1β and IL-18 are key proinflammatory cytokines that play important roles in the pathophysiology of vein graft remodeling. However, the mechanism of IL-1β/IL-18 production and its role in the development of graft remodeling remain unclear. IL-1β/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-1β, 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-1β/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. Our work identified an interaction among necrotic VSMCs, monocytes, and viable VSMCs through IL-1β/IL-18 signaling, which might be exploited as a therapeutic target in vein graft remodeling.