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. Author manuscript; available in PMC: 2021 Jun 9.
Published in final edited form as: Nature. 2020 Dec 9;588(7839):705–711. doi: 10.1038/s41586-020-2998-x

Figure 4. Reelin improves neonatal and adult cardiac function after myocardial infarction.

Figure 4.

a, Echocardiography reveals relatively normal cardiac function at P7 and reduced at P14 and P21 in Reln−/− mice after MI at P2. P7: N=9 (WT), N=9 (Reln+/−), N=10 (Reln−/−); P14: N=10 (WT), N=8 (Reln+/−), N=7 (Reln−/−); P21: N=9 (WT), N=13 (Reln+/−), N=8 (Reln−/−). *p=0.04 (P14) and *p=0.012 (P21) by two-way ANOVA followed by Bonferroni test. b, Masson’s trichrome staining shows increased fibrosis in P21 Reln−/− hearts (MI at P2). Right panel, quantification of the percentage of fibrotic area. N=6 (WT), N=4 (Reln+/−), N=5 (Reln−/−). **p = 0.002 by one-way ANOVA followed by Tukey’s test. c, CM proliferation is decreased in the border of the infarcted area of P7 Reln−/− hearts (N= 4 mice/genotype). *p=0.026 (EdU), *p=0.025 (Ki67), *p=0.022 (pH3) and *p=0.023 (AuroraB) by unpaired two-tailed Student’s t test. d, CM apoptosis increases significantly in the infarcted area of P7 Reln−/− hearts (N= 4 mice/genotype). *p =0.032 by unpaired two-tailed Student’s t test. e, Sutured collagen patch onto the adult mouse heart following MI. f, Residual collagen patch remains up to 42 days after MI. g, Echocardiography reveals significantly improved cardiac function (EF%) in adult mice with REELIN patches starting at around 21 days after MI and up to 42 days post-MI. N=6 (sham), N=6 (control patch) and N=7 (REELIN patch). *p=0.04 (P21), **p=0.001 (P35) and *p=0.01 (P42) by two-way ANOVA followed by Bonferroni test. h, Masson’s trichrome staining shows reduced cardiac fibrotic area in REELIN patch-treated mice 42 days post-MI. Arrowhead shows fibrotic area; arrows indicate residual collagen patch. Right panel, quantification of the percentage of fibrotic area. N=4 (sham), N=4 (control patch), N=6 (REELIN patch). **p = 0.003 by one-way ANOVA followed by Tukey’s test. i, No differences in CM proliferation between control patch and REELIN patch treated hearts were observed in the infarcted areas 7 days post-MI (N = 4 hearts/group). n.s. not significant difference by unpaired two-tailed Student’s t test. j, CM apoptosis is reduced in the infarcted area of REELIN patch treated hearts (N=4 mice/group). *p = 0.039 by unpaired two-tailed Student’s t test. Data are presented as Mean ± S.E.M. Scale bars, 500 μm (b, h). Representative images of c, d, i and j are in Extended Data Fig. 11. Functional parameters for the neonatal and adult MI echocardiography are in Source Data.