Inhibition of microRNA-155 ameliorates cardiac fibrosis in the process of angiotensin II-induced cardiac remodeling

Figures

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  Figure 1.. miR-155 is induced by Ang II treatment in adult C57BL/6 mice. The expression of miR-155 in the (A) heart, (B) spleen and (C) PBMCs of WT adult mice following Ang II infusion for 4 and 8 weeks, as quantified by reverse transcription-quantitative polymerase chain reaction. Data are presented as the mean + standard error of the mean. *P<0.05 and **P<0.01, as indicated. miR, microRNA; Ang, angiotensin; PBMCs, peripheral blood mononuclear cells; WT, wild-type; NS, not significant.

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  Figure 2.. Absence of miR-155 ameliorates the cardiac function following Ang II treatment. (A) Representative images of whole hearts in WT and miR-155 KO groups with or without Ang II treatment. (B) MAP of mice in WT and miR-155 KO groups at different time points during Ang II treatment. (C) Representative M-mode echocardiograms obtained from WT-sham, KO-sham, WT-Ang II and KO-Ang II mice. Echocardiographic measurements of (D) LVDd, (E) LVEF, (F) LVFS and (G) IVS were recorded in WT and KO-sham and Ang II mice. Data are presented as the mean ± standard error of the mean. *P<0.05 and **P<0.01, as indicated. miR, microRNA; Ang, angiotensin; WT, wild-type; KO, knockout; MAP, mean arterial pressure; LVDd, left ventricular diastole diameter; LVEF, left ventricular ejection fraction; LVFS, left ventricular fractional shortening; IVS, interventricular septum diastolic thickness; A, Ang II.

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  Figure 3.. miR-155 deficiency alleviates Ang II-induced cardiac fibrosis (A) Hematoxylin and eosin-stained sections of the left ventricles in miR-155 WT and KO mice. (B) Representative Masson's trichrome staining of cross-sections of left ventricles. Panels A and B: Magnification, ×200 for 4 weeks (sham and +A) and ×100 for 8-weeks [sham and +A(1)]; ×400 for 8-weeks+A(2). (C) Collagen volume fraction in miR-155 WT and KO mice. (D) Representative western blot for α-SMA and collagen I protein expression levels in heart tissues following Ang II treatment for 8 weeks. (E) mRNA expression levels of α-SMA and collagen I in each group at 8 weeks. Data are presented as the mean + standard error of the mean. *P<0.05 and **P<0.01, as indicated. miR, microRNA; Ang, angiotensin; WT, wild-type; KO, knockout; SMA, smooth muscle actin; A, Ang II.

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  Figure 4.. miR-155 regulates fibroblast to myofibroblast transformation in cardiac fibroblasts. The mRNA expression levels of (A) miR-155 and (B) α-SMA in cardiac fibroblasts following Ang II stimulation. (C) miR-155 expression in cells in each group following transfection with miR-155 agomir or antagomir, as determined by reverse transcription-quantitative polymerase chain reaction. mRNA expression levels of (D) α-SMA and (E) collagen I in each group of cardiac fibroblasts. (F) Representative image of western blotting for α-SMA protein expression levels in cardiac fibroblasts from each group. (G) Quantified protein levels of α-SMA in each group. Data are presented as the mean + standard error of the mean. *P<0.05, **P<0.01 and ***P<0.001, as indicated. miR, microRNA; SMA, smooth muscle actin; Ang, angiotensin.

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  Figure 5.. SOCS1 was involved in miR-155-regulated cardiac fibrosis. mRNA expression levels of (A) SOCS1 and (B) SHIP1, which are direct target miR-155 targets, in KO and WT mice heart tissues at 8 weeks. (C and D) mRNA expression levels of TGF-β1 and SMAD3 in heart tissues of KO and WT mice. Data are presented as the mean + standard error of the mean. *P<0.05, **P<0.01 and ***P<0.001, as indicated. SOCS1, suppressor of cytokine signaling 1; miR, microRNA; SHIP1, Src homology 2-containing inositol phosphatase; KO, knockout; WT, wild-type; TGF, transforming growth factor.