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. Author manuscript; available in PMC: 2017 Jul 22.
Published in final edited form as: Circ Res. 2016 Jun 9;119(3):434–449. doi: 10.1161/CIRCRESAHA.116.308700

Figure 7. Grem2 inhibits the pro-inflammatory effect of BMP2 on endothelial cells.

Figure 7

(A) qPCR analysis of whole heart RNA samples isolated from WT mice at days 0, 1, 2, 3, 5 and 7 post-MI shows sequential induction of Tnfα, Bmp2 and Grem2 during the cardiac repair process. * P < 0.05; ** P < 0.01. One-way ANOVA with Dunnett’s multiple comparisons test. N=3 for all time points. All data are means ± SEM. (B) qPCR analysis of RNA samples isolated from Human Microvascular Endothelial Cells (HMEC) at 4 hours (left) and 24 hours (right) after TNFα treatment shows TNFα induces E-SELECTIN and BMP2 expression. * P < 0.05. Student’s two-tailed unpaired t-test. N=3 per group. All data are means ± SEM. (C, D) qPRC analysis shows BMP2 induces E-SELECTIN and GREM2 in HMEC cells after 24 hours. * P < 0.05; **P<0.01. Student’s two-tailed unpaired t-test. N=3 per group. All data are means ± SEM. (E, F) qPCR analysis of RNA sample isolated from HMEC 24 hours after treatment with TNFα, BMP2, Grem2 and DMH1 in different combinations as indicated. (E) TNFα and BMP2 together superinduce expression of E-SELECTIN. Grem2 specifically inhibits the BMP2 effect, but has no effect on the E-SELECTIN induction by TNFα. (F) Canonical BMP signaling inhibitor DMH1 specifically inhibits the BMP2-induced E-SELECTIN. ns=not significant; * P < 0.05; ** P < 0.01; **** P < 0.0001. One-way ANOVA with Dunnett’s multiple comparisons test. N=3 for all treatments. All data are means ± SEM. (G) Adhesion of human monocytes (THP-1 cells) to HMEC cells was measured after HMEC cells incubation with TNFα, BMP2, or in combination for 24 hours. TNFα and BMP2 induce binding of endothelial cells to monocytes. Grem2 specifically inhibits the BMP2 effect. * P < 0.05; **** P < 0.0001. One-way ANOVA with Bonferroni’s multiple comparison test. N=36. All data are means ± SEM.