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Published on: August 8, 2022
Association between miR-181b and PKG 1 in myocardial hypertrophy and its clinical implications
Wei Zhong1, Jun Yang2, Qian Cao3
1Cadre Ward, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277101, P.R. China.
Insights
MicroRNA-181b (miR-181b) is elevated in cardiac hypertrophy and negatively regulates cGMP-dependent protein kinase type I (PKG 1). Inhibiting miR-181b alleviates hypertrophy, suggesting miR-181b as a diagnostic and therapeutic target.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Myocardial hypertrophy is a significant cardiovascular condition.
- The role of microRNAs in cardiac hypertrophy pathogenesis is increasingly recognized.
- cGMP-dependent protein kinase type I (PKG 1) is implicated in cardiac function.
Purpose of the Study:
- To investigate microRNA (miR)-181b expression in myocardial hypertrophy.
- To explore the association between miR-181b and PKG 1 in an in vitro model.
- To assess the potential of miR-181b as a biomarker and therapeutic target.
Main Methods:
- Analysis of miR-181b levels in peripheral blood of patients with myocardial hypertrophy.
- Establishment of an in vitro model of myocardial hypertrophy using phenylephrine (PE) treatment.
- Reverse transcription-quantitative polymerase chain reaction and western blotting to measure gene and protein expression.
Main Results:
- miR-181b expression was upregulated in patients and in vitro models of myocardial hypertrophy.
- PE treatment induced significant cellular hypertrophy and upregulated hypertrophy-related genes.
- A negative correlation was observed between miR-181b and PKG 1 expression; miR-181b inhibition restored PKG 1 and alleviated hypertrophy.
Conclusions:
- miR-181b is upregulated in myocardial hypertrophy and contributes to pathogenesis by regulating PKG 1.
- miR-181b inhibition can alleviate cardiac hypertrophy.
- miR-181b represents a potential molecular indicator for clinical diagnosis and treatment of cardiac hypertrophy.
Abstract:
The aim of this study was to explore the microRNA (miR)-181b expression in myocardial hypertrophy and to investigate its association with cGMP-dependent protein kinase type I (PKG 1) in an in vitro model. The miR-181b level in the peripheral blood was determined in patients with myocardial hypertrophy, and an in vitro model was established via phenylephrine (PE) treatment. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting were performed to detect the expression levels of miR-181b, PKG 1 and hypertrophy-related genes. The results revealed that the expression of miR-181b was elevated in the peripheral blood of patients with myocardial hypertrophy, and this may have contributed to the pathology and progression of the disease. When the primary myocardial cells were treated with PE, microscopic observation and flow cytometry revealed significant hypertrophy. Furthermore, upregulation of myocardial hypertrophy-related genes, including β-myosin heavy chain, α-sarcomeric actinin and atrial natriuretic peptide, was observed. The miR-181b expression level in the PE-treated cells was elevated, while the mRNA and protein expression levels of PKG 1 were decreased, indicating a negative correlation between miR-181b and PKG 1 in myocardial hypertrophy. In addition, when the PE-treated primary myocardial cells were transfected with miR-181b inhibitor, the reduced PKG 1 expression was restored and the myocardial hypertrophy alleviated, as indicated by the reduced cellular sizes and decreased expression levels of the myocardial hypertrophy-related genes. In conclusion, miR-181b expression has been shown to be upregulated in myocardial hypertrophy, and this may play a role in the pathogenesis of the disease by regulating the expression of PKG 1. The present findings suggest that miR-181b is a promising molecular indicator for the clinical diagnosis and treatment of cardiac hypertrophy.
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