Figure 5: Histamine repressed fibroblast proliferation via a histamine receptor-dependent paracrine mechanism.

(a,b) The qRT-PCR and western blotting data showed no expression of HDC in the heart fibroblasts (n = 3). (c) No EGFP expression in the heart fibroblasts of HDC-EGFP mice, as measured by fluorescence microscopy (scale bar = 25 μm). (d) The proliferation rates of neonatal heart fibroblasts of HDC−/− and WT mice at baseline or in hypoxic conditions were measured by the CCK8 assay (n = 6). (e) Histamine (10−5 M~10−4 M) had an inhibitive effect on heart fibroblast proliferation (n = 3). (f) The results of H&E staining showed that the larger infarct size observed in HDC−/− mice could be attenuated by histamine treatment. This effect could be blocked by H1R or H2R antagonists (scale bar = 500 μm; n = 6–8). (g) Masson trichrome staining showed that cardiac fibrosis decreased in histamine-treated HDC−/− mice compared with HDC−/− mice and that this effect was reversed by H1R or H2R antagonists (the top scale bar = 500 μm and other scale bars = 50 μm; n = 6–8). NS, not statistically significant, *p < 0.05, **p < 0.01, ***p < 0.001.