miR-20a regulates pressure overload-induced cardiac hypertrophy

doi:10.12307/2024.107

Abstract

Abstract: BACKGROUND: Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload. It is of compensatory significance in the early stage, but if the stimulation continues, it can cause cardiomyopathy leading to heart failure. MicroRNAs are involved in the regulation of cardiac hypertrophy. However, the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported.
OBJECTIVE: To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms.
METHODS: Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin II was used to induce H9c2 cell models of cardiac hypertrophy in vitro. MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells. Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio, cell surface area, and myocardial fibrosis. The expression levels of atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR. Mitochondrial fission was detected by MitoTracker. The downstream target genes of miR-20a were predicted by RNAhybrid software.
RESULTS AND CONCLUSION: (1) The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts (P < 0.05). (2) At the animal level, overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy, including decreasing the upregulated expression level of hypertrophic marker genes (P < 0.05), reduced the enlarged heart volume, reducing the increased heart weight/body weight ratio (P < 0.01), reducing the increased myocardial cross-sectional area (P < 0.05), and attenuating fibrosis (P < 0.01). (3) At the cellular level, overexpression of miR-20a significantly inhibited angiotensin II-induced cardiomyocyte hypertrophy, including decreasing the upregulated expression levels of atrial natriuretic peptide (P < 0.05), brain natriuretic peptide (P < 0.01) and β-myosin heavy chain (P < 0.05), reducing the increased protein/DNA ratio (P < 0.01), and suppressing the increased cell surface area (P < 0.05). (4) Overexpression of miR-20a significantly inhibited angiotensin II-induced mitochondrial fission (P < 0.05). (5) The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3’ untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved. (6) In conclusion, miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy. Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin II-induced mitochondrial fission.

Key words: miR-20a, cardiac hypertrophy, angiotensin II, transverse aortic constriction, mitochondrial fission

CLC Number:

Sun Teng, Han Yu, Wang Shuang, Li Jialei, Cao Jimin. miR-20a regulates pressure overload-induced cardiac hypertrophy[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(7): 1021-1028.

Figures/Tables 9

References

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