Loss of miR-144 signaling interrupts extracellular matrix remodeling after myocardial infarction leading to worsened cardiac function

Figures

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  Figure 1. miR-144 KO mice develop normally. Cardiac function was represented by ejection fraction (a) and fraction shortening (b). N = 7 for both WT and miR-144. (c) Growth curve. For the WT group N = 17, 10, 12, 11, and 5 for age 4, 8, 12, 16, and 52 weeks accordingly, while N = 11, 10, 10, 12, and 14 for the KO group in the corresponding age time points.

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  Figure 2. Coronary artery ligation induces larger but thinner scar in miR-144 KO mice. (a) Sliced heart. Both Infarction size (b) and scar thickness (c) were determined from images of the PicroSirius stained slides as detailed in the Methods. *p < 0.05 compared with WT, N = 7 for WT and 6 for miR-144 KO.

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  Figure 3. miR-144 KO modifies ECM remodeling post MI. (a) Left ventricular collagen contents. *P < 0.05 compared with WT, N = 6 for WT and 7 for miR-144 KO. (b). Collagen cross linkage. #p < 0.01 compared with WT, N = 6 for WT and 7 for miR-144 KO. (c) Collagen cross linkage corrected by collagen content. #p < 0.01 compared with WT, N = 6 for WT and 7 for miR-144 KO. (d) Collagen networks. Pictures are representive of images from 7 mice in the WT group and 6 mice in the miR-144 KO group.

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  Figure 4. miR-144 knocks down LOX1 protein levels. LOX1 protein levels were determined by Western blot from the hearts of mice which underwent MI 7 days previously (a). Cardiac LOX1 levels were also determined from mice injected with miR-144 (b) and miR-144 KO mice without MI (c). *p < 0.05 and #p < 0.01 compared with WT or CONT which is PBS injection. N = 6 for WT and miR-144 KO in panel a; N = 4 for both miR-144 and PBS injection in panel b; and N = 5 for both WT and miR-144 KO in panel c.

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  Figure 5. miR-144 targets Zeb1 in the heart. (a) miR-144 targets in Zeb1 mRNA untranslated region. Cardiac Zeb1 Protein levels were determined by Western blot from WT mice after myocardial infarction (b), miR-144 KO mice without MI (c), and miR-144 injection (d). *p < 0.05 and #p < 0.01 compared with WT or CONT which is PBS injection. N = 6 for WT and miR-144 KO in panel b; N = 5 for both miR-144 KO and WT in panel c; and N = 4 for both miR-144 injection and CONT in panel d.

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  Figure 6. LOX1 is positively correlated with Zeb1 in cultured neonatal cardiac fibroblasts. Both Zeb1 (a) and LOX1 (b) were induced by TGFβ but suppressed by DOXO (doxorubicin). #p < 0.01 compared with CONT, N = 4 for both panel a and b.

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  Figure 7. miR-144 KO interferes with the healing process post MI leading to worsened cardiac function. (a) Acute cardiac rupture post MI. N = 31 for WT and 49 for miR-144 KO. (b) Heart and body weight ratio. *p < 0.05 compared with WT. N = 13 for both WT and miR-144 KO. (c) Represent images of echocardiography. (d) Ejection fraction. #p < 0.01 compared with WT. N = 13 for WT and miR-144 KO. (e) Fraction shortening. *p < 0.05 compared with WT. N = 13 for WT and miR-144.