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. 2020 Sep 30;40(9):BSR20201696.
doi: 10.1042/BSR20201696.

MicroRNA-132 attenuated cardiac fibrosis in myocardial infarction-induced heart failure rats

Guoyu Wang  1 , Ruzhu Wang  1 , Zhongbao Ruan  1 , Ling Liu  1 , Yong Li  2 , Li Zhu  1
Affiliations

MicroRNA-132 attenuated cardiac fibrosis in myocardial infarction-induced heart failure rats

Guoyu Wang et al. Biosci Rep. .

Abstract

The aim of the present study was to determine the effect of microRNA (miR)-132 on cardiac fibrosis in myocardial infarction (MI)-induced heart failure and angiotensin (Ang) II-treated cardiac fibroblasts (CFs). Experiments were carried out in Sprague-Dawley rat treatment with ligation of left coronary artery to induce heart failure, and in CFs administration of Ang II to induce fibrosis. The level of miR-132 was increased in the heart of rats with MI-induced heart failure and the Ang II-treated CFs. In MI rats, left ventricle (LV) ejection fraction, fractional shortening, the maximum of the first differentiation of LV pressure (LV +dp/dtmax) and decline (LV -dp/dtmax) and LV systolic pressure (LVSP) were reduced, and LV end-systolic diameter (LVESD), LV end-diastolic diameter (LVEDD), LV volumes in systole (LVVS) and LV volumes in diastole (LVVD) were increased, which were reversed by miR-132 agomiR but deteriorated by miR-132 antagomiR. The expression levels of collagen I, collagen III, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) were increased in the heart of rat with MI-induced heart failure and CFs administration of Ang II. These increases were inhibited by miR-132 agomiR but enhanced by miR-132 antagomiR treatment. MiR-132 inhibited PTEN expression, and attenuated PI3K/Akt signal pathway in CFs. These results indicated that the up-regulation of miR-132 improved the cardiac dysfunction, attenuated cardiac fibrosis in heart failure via inhibiting PTEN expression, and attenuating PI3K/Akt signal pathway. Up-regulation of miR-132 may be a strategy for the treatment of heart failure and cardiac fibrosis.

Keywords: cardiac dysfunction; cardiac fibroblasts; fibrosis; heart failure; microRNA -132.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Expression of microRNA (miR)-132
(A) The level of miR-132 was reduced in the heart of myocardial infarction (MI)-induced heart failure rats. (B) MiR-132 expression level was reduced in the heart of rat administration of angiotensin (Ang) II. (C) MiR-132 expression level was reduced in Ang II-treated cardiac fibroblasts (CFs). (D) MiR-132 expression level was increased in the heart of rat treatment with miR-132 agomiR. (E) MiR-132 expression level was reduced in the heart of rat treatment with miR-132 antagomiR. The results are expressed as mean ± SE; N =8; *P<0.05 versus the Sham group (A) or PBS group (B).
Figure 2
Figure 2. Effects of microRNA (miR)-132 agomiR on cardiac function in myocardial infarction (MI)-induced heart failure rats
The left ventricular (LV) ejection fraction (EF) and fractional shortening (FS) were reduced, and LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), LV volumes in systole diastole (LVVs) and LV volumes in diastole (LVVd) were increased in MI-induced heart failure rats. These changes were reversed by miR-132 agomiR treatment. The results are expressed as mean ± SE; N=8; *P<0.05 versus the Sham+NC agomiR group; #P<0.05 versus the MI+NC agomiR group.
Figure 3
Figure 3. Effects of microRNA (miR)-132 antagomiR on cardiac function in myocardial infarction (MI)-induced heart failure rats
The left ventricular (LV) ejection fraction (EF) and fractional shortening (FS) were reduced, and LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), LV volumes in systole diastole (LVVs) and LV volumes in diastole (LVVd) were increased in MI-induced heart failure rats, and these changes were further aggravated by miR-132 antagomiR treatment. The results are expressed as mean ± SE; N=8; *P<0.05 versus the Sham+NC antagomiR group; #P<0.05 versus the MI+NC antagomiR group.
Figure 4
Figure 4. Effects of microRNA (miR)-132 agomiR on cardiac hemodynamics in myocardial infarction (MI)-induced heart failure rats
The maximum of the first differentiation of left ventricular pressure (LV +dp/dtmax) and decline (LV -dp/dtmax) and left ventricle systolic pressure (LVSP) were reduced, and LV end-diastolic pressure (LVEDP) was increased in MI-induced heart failure rats, and these changes were reversed by miR-132 agomiR treatment. The results are expressed as mean ± SE; N=8; *P<0.05 versus the Sham+NC agomiR group; #P<0.05 versus the MI+NC agomiR group.
Figure 5
Figure 5. Effects of microRNA (miR)-132 antagomiR on cardiac hemodynamics in myocardial infarction (MI)-induced heart failure rats
The maximum of the first differentiation of left ventricular pressure (LV +dP/dtmax) and decline (LV -dP/dtmax) and left ventricle systolic pressure (LVSP) were reduced, and LV end-diastolic pressure (LVEDP) was increased in MI-induced heart failure rats, and these changes were further aggravated by miR-132 antagomiR treatment. The results are expressed as mean ± SE; N=8; *P<0.05 versus the Sham+NC antagomiR group; #P<0.05 versus the MI+NC antagomiR group.
Figure 6
Figure 6. Effects of microRNA (miR)-132 agomiR on cardiac fibrosis in myocardial infarction (MI)-induced heart failure rats
(A) The increase of fibrosis in heart was inhibited by miR-132 agomiR treatment. (B) The expression levels of collagen I, collagen III, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) were increased in the heart of MI-induced heart failure rats, and these increases were inhibited by miR-132 agomiR treatment; N=8; *P<0.05 versus the Sham+NC agomiR group; #P<0.05 versus the MI+NC agomiR group.
Figure 7
Figure 7. Effects of microRNA (miR)-132 antagomiR on cardiac fibrosis in myocardial infarction (MI)-induced heart failure rats
The expression levels of collagen I, collagen III, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) were increased in the heart of MI-induced heart failure rats, and these increases were further enhanced by miR-132 antagomiR treatment; N=8; *P<0.05 versus the Sham+NC antagomiR group; #P<0.05 versus the MI+NC antagomiR group.
Figure 8
Figure 8. Effects of microRNA (miR)-132 agomiR on fibrosis in cardiac fibroblasts (CFs) treated with angiotensin (Ang) II
The expression levels of collagen I, collagen III, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) were increased in Ang II-treated CFs, and these increases were inhibited by miR-132 agomiR treatment. *P<0.05 versus the PBS+NC agomiR group; #P<0.05 versus the Ang II+NC agomiR group.
Figure 9
Figure 9. Effects of microRNA (miR)-132 antagomiR on the fibrosis of cardiac fibroblasts (CFs) treated with angiotensin (Ang) II
The expression levels of collagen I, collagen III, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) were increased in Ang II-treated CFs, and these increases were further enhanced by miR-132 antagomiR treatment. *P<0.05 versus the PBS+NC antagomiR group; #P<0.05 versus the Ang II+NC antagomiR group.
Figure 10
Figure 10. The mechanism of miR-132
(A) The luciferase activity of PTEN-WT 3′-UTR was markedly attenuated by miR-132 agimiR. (B–D) The increases of p-PI3K and p-Akt were inhibited by miR-132 agomiR. *P<0.05 versus the NC agomiR (A) or PBS+NC agomiR (B) group; #P<0.05 versus the Ang II+NC agomiR group.
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