Over-expression of microRNA-145 drives alterations in β-adrenergic signaling and attenuates cardiac remodeling in heart failure post myocardial infarction

Liu, Zhebo; Bo, Tao; Fan, Suzhen; Cui, Shengyu; Pu, Yuehua; Qiu, Liqiang; Xia, Hao; Xu, Lin

doi:10.18632/aging.103320

Cited by 14 publications

(3 citation statements)

References 53 publications

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“…CaMKIIδ mRNA was analysed by PCR, and the results showed that CaMKIIδ mRNA expression in the model group was increased, which was consistent with the conclusion of Sag C M et al [51]. Propranolol can reduce the expression level of CaMKIIδ, indicating that propranolol reduces the expression and activity of CaMKII by improving oxidative stress and regulating CaMKIIδ mRNA expression.…”

Section: Discussionsupporting

confidence: 84%

The Mechanism of Isoproterenol Hydrochloride-Induced Cardiac Arrhythmia and the Effect of Propranolol Through the CaMKII Pathway

Ma,

et al. 2023

Preprint

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Background Ventricular arrhythmia (VA) is a common clinical disease that is associated with high morbidity and mortality. Calcium/calmodulin-dependent protein kinase II (CaMKII) is critical in regulating cardiac electrophysiological functions. Research shows that propranolol can significantly antagonizes VA. However, it is unclear whether propranolol can regulate CaMKII, thereby inhibiting VA. Aims The present study aimed to clarify the molecular mechanism by which propranolol inhibits VA through the CaMKII pathway. Methods A total of 60 healthy Sprague Dawley rats were randomly divided into the control and experimental groups (model and propranolol group) that were given corresponding treatment. Isoproterenol hydrochloride (ISO) was administered to induce VA. The ECG was monitored for 1 hour, and the VA incidence was calculated. The heart weight/body weight (HW/BW) ratio was calculated manually. The levels of Ca2+, cTnI, oxidative stress, Inflammatory factors were studied.Calcium pump (SERCA2) and CaMKIIδ mRNA were detected by Real-time PCR. Western blotting was used to assess CaMKII, oxidized CaMKII (OX-CaMKII), phosphorylated phosphoprotein (P-PLB) and SERCA2. Results There was no obvious abnormality in the control group. Compared with the control group rats, the indexes of rats in model group changed significantly (P < 0.01). Compared with the model group rats, the indexes of rats in the propranolol was significantly improved (P < 0.01 or P < 0.05 ). Conclusions Collectively, propranolol antagonized VA effect by reducing CaMKII expression and activating SERCA2, thereby reducing the Ca2 + load .

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Section: Discussionsupporting

confidence: 84%

The Mechanism of Isoproterenol Hydrochloride-Induced Cardiac Arrhythmia and the Effect of Propranolol Through the CaMKII Pathway

Ma,

et al. 2023

Preprint

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“…After adaptive feeding, the rat model of MI was established by ligating the left anterior descending coronary artery using the method described by Liu et al . [ 8 ]: The rats were anesthetized by intraperitoneal injection of pentobarbital sodium (45 mg/kg), and fixed on an operating table in the supine position, with the limbs connected to an electrocardiograph. After skin preparation on the left chest and trachea and disinfection with iodophor, the neck was cut open to expose the trachea, and a ventilator was connected.…”

Section: Methodsmentioning

confidence: 99%

Protective role of emodin in rats with post-myocardial infarction heart failure and influence on extracellular signal-regulated kinase pathway

Liu¹,

Liang²

2021

Bioengineered

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We aimed to explore the effects of emodin on the energy metabolism of myocardial cells in rats with post-myocardial infarction (MI) heart failure (HF) and the extracellular signal-regulated kinase (ERK) pathway. The model of MI was established by ligation of the left anterior descending branch. After 4 weeks, the rats with left ventricular ejection fraction (LVEF) of ≤45% were used aspost-MI HF model animals and randomly divided into model, low-dose, middle-dose, high-dose and control groups (n=10). Low-, middle- and high-dose groups were gavaged with 20 mg/kg, 40 mg/kg and 60 mg/kg emodin daily, respectively. After administration for 14 d, the changes in LVEF, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD) and interventricular septum thickness (IVS) were analyzed. The apoptosis rate of myocardial cells was detected by TUNEL staining. The levels of serum cardiac troponin I (cTnI) and peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) were determined using ELISA, and the expressions of mitochondrial respiratory chain complex I protein and phosphorylated-ERK (p-ERK) in myocardial tissues were determined by Western blotting. Compared with model group, LVEDD, LVESD, apoptosis rate of myocardial cells, levels of serum cTnI and PGC-1, and expressions of complex I and p-ERK in myocardial tissues significantly decreased, while LVEF and IVS increased in low-dose, middle-dose, high-dose and control groups (P<0.05). The changes in the above indices were significantly dependent on the dose of emodin (P<0.05).Emodin can significantly relieve post-MI HF, reduce the apoptosis rate of myocardial tissues, and ameliorate the cardiac function of rats.

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“…Studies have shown that miR-133 regulates multiple components of β 1 -AR signaling and has a cardioprotective effect by reducing apoptosis and fibrosis in pressure overload-induced heart failure [106]. miR-145 improves cardiac dilatation and fibrosis and alleviates heart failure-related cardiac remodeling by upregulating β 2 -ARs and downregulating CaMKII [107]. Downregulation of non-coding RNA circ-HIPK3 attenuates fibrosis and maintains myocardial function after myocardial infarction in mice through miR-17-3p [108].…”

Section: Other Regulatory Mechanisms Of β-Ar Signaling In the Heartmentioning

confidence: 99%

Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease

Song

WOO²,

Zhang³

et al. 2022

IJDDP

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Review Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease Ying Song 1, Anthony Yiu-Ho Woo 2,*, Yan Zhang 3,4,*, and Ruiping Xiao 5,6,7,8 1 Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China. 2 School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China. 3 Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, School of Basic Medical Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China. 4 Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China. 5 State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, 100871, China. 6 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. 7 Beijing City Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, 100871, China. 8 PKU-Nanjing Joint Institute of Translational Medicine, Nanjing, 210000, China. * Correspondence: yiuhowoo@syphu.edu.cn (Anthony Yiu-Ho Woo), Tel.: +86-24-23986375; zhangyan9876@pku.edu.cn (Yan Zhang), Tel.: +86-10-82805945. Received: 19 October 2022 Accepted: 28 October 2022 Published: 21 December 2022 Abstract: A variety of G protein-coupled receptors (GPCRs) are involved in the regulation of cardiovascular function. The β-adrenoceptors (β-ARs), with three subtypes, are the dominant receptor species in the heart, in which the β1-AR and the β2-AR are considered functional. Stimulation of the β-ARs produces myocardial inotropy via activation of the Gs-cAMP-PKA signaling cascade. Prolonged stimulation of the β1-AR is cardiac harmful because the stimulated β1-AR couples only to Gs proteins and it mediates a cardiotoxic signal. On the other hand, the β2-AR couples dually to both Gs and Gi proteins and the β2-AR-Gi pathway is antiapoptotic. The activated Gi signal also counteracts the β-AR-Gs-promoted positive inotropic effect. Other key players in cardiac β-AR signaling include Ca2+/calmodulin-dependent protein kinases (CaMKs), GPCR kinases (GRKs), β-arrestins and phosphodiesterases. During heart failure, excessive sympathetic stimulation results in the activation of the cardiotoxic β1-AR-CaMKIIδ pathway and the upregulation of GRK2 and Gi in the heart. GRK2 promotes the desensitization of β-ARs and enhances a β2-AR-mediated Gi signaling. These signal transduction processes accompanying the downregulation of the β1-AR are involved in cardiac dysfunction, maladaptive cardiac remodeling, and the progression of chronic heart failure. β-Blockers are widely used in the treatment of cardiovascular disease. They have established their position as one of the “four pillars of heart failure” thirty years ago. In the present review, we provide an overview of the recent progress in the basic research of GPCRs focusing on cardiac β-AR signal transduction.

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Over-expression of microRNA-145 drives alterations in β-adrenergic signaling and attenuates cardiac remodeling in heart failure post myocardial infarction

Cited by 14 publications

References 53 publications

The Mechanism of Isoproterenol Hydrochloride-Induced Cardiac Arrhythmia and the Effect of Propranolol Through the CaMKII Pathway

The Mechanism of Isoproterenol Hydrochloride-Induced Cardiac Arrhythmia and the Effect of Propranolol Through the CaMKII Pathway

Protective role of emodin in rats with post-myocardial infarction heart failure and influence on extracellular signal-regulated kinase pathway

Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease

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