Abstract 16296: The Contribution of Macrophage Subpopulations During Collateral Growth
Arterial occlusion leads to growth of collaterals, in which macrophages (MAC) play a prominent role. However, a detailed analysis which MAC-subpopulations are involved in arteriogenesis has never been performed. In the present study the temporal and spatial distribution of MAC subtypes during arteriogenesis was investigated. Rats (n=42) were subjected to Femoral Arterial Ligation (FAL) and shunting of the femoral artery with the accompanying vein distal to the ligature. Local MAC-subpopulations were phenotyped using CD68 and CD163 12h, 1d, 3d, 7d, 14d and 28d after surgery. For analysis of circulating monocytes by FACS, male C-57/bl-6 mice were divided in 3 groups (n=3 each), receiving either double sham, FAL and sham or FAL on both hind limbs. Three groups of mice (n=8 each) received PBS (controls), dexamethasone (DEX, 50 mg/kg BW) or interleukin 10 (IL10, 20 ng/kg BW) 2d, 4d and 6d after FAL. Perfusion measurements were performed by Laser-Doppler-Imaging. In rats without occlusion, only M2-MAC reside in the perivascular space (12.5+/-4 pos. cells/vessel, n=18). Early after occlusion (12h), the number of M2-MAC increases strongly (26.4+/-2.6; n=18; p<0.05) compared to sham controls (14.9+/-3.9 pos. cells/vessel, n=18). M1-MAC initially only increase slightly, compared to those in the untreated rats (3.6+/-1.9 vs. 0.9+/-0.8 pos. cells/vessel, n=18). At later time points both subpopulations further increased. The local distribution of the subpopulations changes during the arteriogenic process. Whereas M1-MAC are detected adjacent to the media, M2-MAC are present in the outer perivascular region of collateral vessel. Subpopulations of circulating monocytes were not altered during arteriogenesis in mice. Suppressing inflammatory monocytes (M1) with DEX impaires perfusion recovery (36+/-7 % vs. 61+/-9 % in sham controls; n=5; p<0.005), whereas IL10 application significantly increases perfusion (81+/-5 %; n=5; p<0.05). The distinct early increase and spatial distribution of M2-MAC support the idea that this subtype plays a predominant role during collateral remodelling and demonstrates that a forced shift towards M2-MAC improves arteriogenesis.
- © 2012 by American Heart Association, Inc.