FIGURE 5.

Gremlin-1 reduces the number of monocytes/macrophages in atherosclerotic plaques and attenuates atheroprogression in ApoE^−/− mice. a, experimental protocol for the treatment and feeding of ApoE^−/− mice. _mGremlin-1-Fc (1 μg/g body weight) (n = 8) or equimolar Fc control (0.6 μg/g body weight) (n = 8) was injected intraperitoneally 3 times/week into 10-week-old mice for 4 weeks. b, _mGremlin-1-Fc substantially reduced the number and cell size of CD68-positive cells in atherosclerotic lesions. Representative immunostainings of CD68 expression and H&E staining of atherosclerotic aortic tissue of _mGremlin-1-Fc and Fc-treated ApoE^−/− mice are shown. Data represent the mean ± S.E. of eight mice (*, p < 0.05). c, administration of _mGremlin-1-Fc reduced TNF-α, MIF, and Mac-3 expression in aortic plaques. Representative immunostainings of TNF-α, MIF, and Mac-3 of atherosclerotic aortic tissue in _mGremlin-1-Fc and Fc-treated ApoE^−/− mice are shown. d, _mGremlin-1-Fc reduces atherosclerotic plaque extension. Representative photographs of H&E staining of aortic root sections (two upper left micrographs) and Sudan red III-stained aortic arches and thoracic aortas (two central and lower left macroscopic photographs) as well as quantitative analysis of the plaque extension (right panel) are shown. The mean percentages of plaque areas in relation to total vessel areas of all mice are shown with mean ± S.E. (n = 8 for each group). (*, p < 0.05, statistical significance).