scholarly journals Qiliqiangxin Attenuates Phenylephrine-Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p

2016 ◽  
Vol 38 (5) ◽  
pp. 1743-1751 ◽  
Author(s):  
Haifeng Zhang ◽  
Shanshan Li ◽  
Qiulian Zhou ◽  
Qi Sun ◽  
Shutong Shen ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Neonatal Rat ◽  
Immunofluorescent Staining ◽  
Mouse Heart ◽  
Mrna Levels ◽  
Elevated Protein ◽  
Ischemic Stress

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has long been used to treat chronic heart failure. Previous studies demonstrated that QL could prevent cardiac remodeling and hypertrophy in response to hypertensive or ischemic stress. However, little is known about whether QL could modulate cardiac hypertrophy in vitro, and (if so) whether it is through modulation of specific hypertrophy-related microRNA. Methods: The primary neonatal rat ventricular cardiomyocytes were isolated, cultured, and treated with phenylephrine (PE, 50 µmol/L, 48 h) to induce hypertrophy in vitro, in the presence or absence of pretreatment with QL (0.5 µg/ml, 48 h). The cell surface area was determined by immunofluorescent staining for α-actinin. The mRNA levels of hypertrophic markers including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (MYH7) were assayed by qRT-PCRs. The protein synthesis of cardiomyocytes was determined by the protein/DNA ratio. The miR-199a-5p expression level was quantified in PE-treated cardiomyocytes and heart samples from acute myocardial infarction (AMI) mouse model. MiR-199a-5p overexpression was used to determine its role in the anti-hypertrophic effect of QL on cardiomyocytes. Results: PE induced obvious enlargement of cell surface in cardiomyocytes, paralleling with increased ANP, BNP, and MYH7 mRNA levels and elevated protein/DNA ratio. All these changes were reversed by the treatment with QL. Meanwhile, miR-199a-5p was increased in AMI mouse heart tissues. Of note, the increase of miR-199a-5p in PE-treated cardiomyocytes was reversed by the treatment with QL. Moreover, overexpression of miR-199a-5p abolished the anti-hypertrophic effect of QL on cardiomyocytes. Conclusion: QL prevents PE-induced cardiac hypertrophy. MiR-199a-5p is increased in cardiac hypertrophy, while reduced by treatment with QL. miR-199a-5p suppression is essential for the anti-hypertrophic effect of QL on cardiomyocytes.

scholarly journals Myricetin Alleviates Pathological Cardiac Hypertrophy via TRAF6/TAK1/MAPK and Nrf2 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Hai-han Liao ◽  
Nan Zhang ◽  
Yan-yan Meng ◽  
Hong Feng ◽  
Jing-jing Yang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Mapk Signaling ◽  
Neonatal Rat ◽  
Mouse Heart ◽  
Pathological Cardiac Hypertrophy ◽  
Pathological Hypertrophy ◽  
Nrf2 Signaling Pathway

Myricetin (Myr) is a common plant-derived polyphenol and is well recognized for its multiple activities including antioxidant, anti-inflammation, anticancer, and antidiabetes. Our previous studies indicated that Myr protected mouse heart from lipopolysaccharide and streptozocin-induced injuries. However, it remained to be unclear whether Myr could prevent mouse heart from pressure overload-induced pathological hypertrophy. Wild type (WT) and cardiac Nrf2 knockdown (Nrf2-KD) mice were subjected to aortic banding (AB) surgery and then administered with Myr (200 mg/kg/d) for 6 weeks. Myr significantly alleviated AB-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction in both WT and Nrf2-KD mice. Myr also inhibited phenylephrine- (PE-) induced neonatal rat cardiomyocyte (NRCM) hypertrophy and hypertrophic markers’ expression in vitro. Mechanically, Myr markedly increased Nrf2 activity, decreased NF-κB activity, and inhibited TAK1/p38/JNK1/2 MAPK signaling in WT mouse hearts. We further demonstrated that Myr could inhibit TAK1/p38/JNK1/2 signaling via inhibiting Traf6 ubiquitination and its interaction with TAK1 after Nrf2 knockdown in NRCM. These results strongly suggested that Myr could attenuate pressure overload-induced pathological hypertrophy in vivo and PE-induced NRCM hypertrophy via enhancing Nrf2 activity and inhibiting TAK1/P38/JNK1/2 phosphorylation by regulating Traf6 ubiquitination. Thus, Myr might be a potential strategy for therapy or adjuvant therapy for malignant cardiac hypertrophy.

Abstract P194: CCAAT/Enhancer-Binding Protein Beta Negatively Regulates Hemodynamic Stress-Induced Cardiac Hypertrophy

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Jota Oyabu ◽  
Osamu Yamaguchi ◽  
Takafumi Oka ◽  
Shungo Hikoso ◽  
Kazuhiko Nishida ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Heart Development ◽  
Protein Isoforms ◽  
Neonatal Rat ◽  
Luciferase Reporter ◽  
Mouse Heart ◽  
Mrna Levels ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy ◽  
Gene Assay

The CCAAT/enhancer-binding proteins (C/EBP) beta is a member of family of leucine-zipper transcription factors that regulate gene expression to control cellular proliferation, differentiation, inflammation and metabolism. Previous reports showed that the protein and mRNA levels of C/EBP beta were increased in rat ischemia-reperfused or human failing hearts. Recent study indicates an important role of C/EBP beta in physiological cardiac hypertrophic responses. In the present study, we generated cardiac-specific C/EBP beta-deficient mice (CKO) to elucidate its in vivo function in pathological cardiac hypertrophy. We crossed floxed C/EBP beta mice with mice expressing Cre recombinase in cardiac-specific manner. Echocardiographic and physiological analyses revealed that CKO showed no cardiac phenotypes under basal conditions at 10 weeks old, indicating that the C/EBP beta is not essential for mouse heart development. Then, we subjected CKO and control mice (CTL) to pressure overload by means of transverse aortic constriction (TAC). In wild-type mouse hearts, the expression level of C/EBP beta was increased after TAC. One week after TAC, CKO showed left ventricle (LV) hypertrophy (LV/body weight, CKO 4.64 ± 0.08 mg/g versus CTL 4.14 ± 0.06 mg/g, p<0.01, LV mass index, CKO 106.1 ± 1.7 versus CTL 98.5 ± 1.8, p<0.05), without showing contractile dysfunction. Cross-sectional area of cardiomyocytes was increased in CKO after TAC (CKO 373.6 ± 2.1 μm 2 versus CTL 300.5 ± 3.6 μm 2 , p<0.01). The increase in the atrial natriuretic factor (ANF) or alpha skeletal actin mRNA expression, molecular markers for cardiac remodeling, was observed in CKO hearts. Furthermore, overexpression of C/EBP beta in isolated neonatal rat cardiomyocytes inhibited an increase in 3 H-leucine uptake induced by phenylephrine stimulation. C/EBP beta is expressed as three distinct protein isoforms, namely FL, LAP, and LIP, which are encoded by a single gene, but transcribed from different initiation sites. Luciferase reporter gene assay showed that overexpression of LAP isoform attenuated the transcriptional activity of ANF induced by phenylephrine, but not LIP. Thus, we conclude that C/EBP beta attenuates the pathological cardiac hypertrophy induced by hemodynamic stresses.

scholarly journals Betulinic Acid Protects DOX-Triggered Cardiomyocyte Hypertrophy Response through the GATA-4/Calcineurin/NFAT Pathway

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 53
Author(s):  
Jung Joo Yoon ◽  
Chan Ok Son ◽  
Hye Yoom Kim ◽  
Byung Hyuk Han ◽  
Yun Jung Lee ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Betulinic Acid ◽  
Cardiomyocyte Hypertrophy ◽  
Ros Generation ◽  
H9c2 Cells ◽  
Myosin Light Chain 2 ◽  
Cardiovascular Morbidity And Mortality

Cardiac hypertrophy is a major risk factor for heart failure and leads to cardiovascular morbidity and mortality. Doxorubicin (DOX) is regarded as one of the most potent anthracycline antibiotic agents; however, its clinical usage has some limitations because it has serious cardiotoxic side effects such as dilated cardiomyopathy and congestive heart failure. Betulinic acid (BA) is a pentacyclic-cyclic lupane-type triterpene that has been reported to have anti-bacterial, anti-inflammatory, anti-vascular neogenesis, and anti-fibrotic effects. However, there is no study about its direct effect on DOX induced cardiac hypertrophy and apoptosis. The present study aims to investigate the effect of BA on DOX-induced cardiomyocyte hypertrophy and apoptosis in vitro in H9c2 cells. The H9c2 cells were stimulated with DOX (1 µM) in the presence or absence of BA (0.1–1 μM) and incubated for 24 h. The results of the present study indicated that DOX induces the increase cell surface area and the upregulation of hypertrophy markers including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), beta-myosin heavy chain (β-MHC), and Myosin Light Chain-2 (MLC2) in H9c2 cells. However, the pathological hypertrophic responses were downregulated after BA treatment. Moreover, phosphorylation of JNK, ERK, and p38 in DOX treated H9c2 cells was blocked by BA. As a result of measuring the change in ROS generation using DCF-DA, BA significantly inhibited DOX-induced the production of intracellular reactive oxygen species (ROS) when BA was treated at a concentration of over 0.1 µM. DOX-induced activation of GATA-4 and calcineurin/NFAT-3 signaling pathway were remarkably improved by pre-treating of BA to H9c2 cells. In addition, BA treatment significantly reduced DOX-induced cell apoptosis and protein expression levels of Bax and cleaved caspase-3/-9, while the expression of Bcl-2 was increased by BA. Therefore, BA can be a potential treatment for cardiomyocyte hypertrophy and apoptosis that lead to sudden heart failure.

Alteration of Atrial Natriuretic Peptide and Brain Natriuretic Peptide Gene Expression Associated with Progression and Regression of Cardiac Hypertrophy in Renovascular Hypertensive Rats

1996 ◽  
Vol 90 (3) ◽  
pp. 197-204 ◽  
Author(s):  
Hideo Kawakami ◽  
Hideki Okayama ◽  
Mareomi Hamada ◽  
Kunio Hiwada
Keyword(s):  
Gene Expression ◽  
Atrial Natriuretic Peptide ◽  
Cardiac Hypertrophy ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Mrna Levels ◽  
Hypertensive Rats ◽  
Regression Of Cardiac Hypertrophy ◽  
Peptide Gene ◽  
Atrial Natriuretic

1. We assessed the changes of atrial natriuretic peptide and brain natriuretic peptide gene expression associated with progression and regression of cardiac hypertrophy in renovascular hypertensive rats (RHR). 2. Two-kidney, one-clip hypertensive rats (6-week-old male Wistar) were made and studied 6 (RHR-1) and 10 weeks (RHR-2) after the procedure. Regression of cardiac hypertrophy was induced by nephrectomy at 6 weeks after constriction, and the nephrectomized rats were maintained further for 4 weeks (nephrectomized rat: NEP). Sham operation was performed, and the rats were studied after 6 (Sham-1) and 10 weeks (Sham-2). Atrial natriuretic peptide and brain natriuretic peptide gene expression in the left ventricle was analysed by Northern blotting. 3. Plasma atrial natriuretic peptide and brain natriuretic peptide were significantly higher in RHR-1 and RHR-2 than in Sham-1, Sham-2 and NEP. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in RHR-1 were approximately 7.2-fold and 1.8-fold higher than those in Sham-1, respectively, and the corresponding levels in RHR-2 were 13.0-fold and 2.4-fold higher than those in Sham-2, respectively. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels of NEP were normalized. Levels of atrial natriuretic peptide and brain natriuretic peptide mRNA were well correlated positively with left ventricular weight/body weight ratios. There was a significant positive correlation between the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA (r = 0.86, P<0.01). 4. We conclude that the expression of atrial natriuretic peptide and brain natriuretic peptide genes is regulated in accordance with the degree of myocardial hypertrophy and that the augmented expression of these two natriuretic peptides may play an important role in the maintenance of cardiovascular haemodynamics in renovascular hypertension.

Abstract 124: Function of the Cytoskeletal Proteins Alpha-catenins in Myocardial Growth Control

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Jifen Li ◽  
Sarah Carrante ◽  
Roslyn Yi ◽  
Frans van Roy ◽  
Glenn L. Radice
Keyword(s):  
Heart Development ◽  
Growth Control ◽  
Cytoskeletal Proteins ◽  
Neonatal Rat ◽  
Nuclear Accumulation ◽  
Mouse Heart ◽  
Cardiomyocyte Proliferation ◽  
Rat Cardiomyocytes ◽  
Neonatal Cardiomyocytes

Introduction: Mammalian heart possesses regenerative potential immediately after birth and lost by one week of age. The mechanisms that govern neonatal cardiomyocyte proliferation and regenerative capacity are poorly understood. Recent reports indicate that Yap-Tead transcriptional complex is necessary and sufficient for cardiomyocyte proliferation. During postnatal development, N-cadherin/catenin adhesion complex becomes concentrated at termini of cardiomyocytes facilitating maturation of a specialized intercellular junction structure, the intercalated disc (ICD). This process coincides with the time cardiomyocytes exit cell cycle soon after birth. Hypothesis: We hypothesize that coincident with maturation of ICD α-catenins sequester transcriptional coactivator Yap in cytosol thus preventing activation of genes critical for cardiomyocyte proliferation. Methods: We deleted αE-catenin / αT-catenin genes (α-cat DKO) in perinatal mouse heart and knockdown (KD) α-catenins in neonatal rat cardiomyocytes to study functional impact of α-catenins ablation on ICD maturation. Results: We previously demonstrated that adult α-cat DKO mice exhibited decrease in scar size and improved function post myocardial infarction. In present study, we investigated function of α-catenins during postnatal heart development. We found increase in the number of Yap-positive nuclei (58.7% in DKO vs. 35.8 % in WT, n=13, p<0.001) and PCNA (53.9% in DKO vs. 47.8%, n=8, p<0.05) at postnatal day 1 and day 7 of α-cat DKO heart, respectively. Loss of α-catenins resulted in reduction in N-cadherin at ICD at day 14. We observed an increase number of mononucleated myocytes and decrease number of binucleated myocytes in α-cat DKO compared to controls. Using siRNA KD, we were able to replicate α-cat DKO proliferative phenotype in vitro. The number of BrdU-positive cells was decreased in α-cat KD after interfering with Yap expression (2.91% in α-cat KD vs. 2.02% in α-cat/Yap KD, n>2500 cells, p<0.05), suggesting α-catenins regulate cell proliferation through Yap in neonatal cardiomyocytes. Conclusion: Our results suggest that maturation of ICD regulates α-catenin-Yap interactions in cytosol, thus preventing Yap nuclear accumulation and cardiomyocyte proliferation.

Abstract 2423: B-type Natriuretic Peptide Upregulates Erythropoietin Receptor Gene Expression via Protein Kinase G in Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yoshiaki Ohyama ◽  
Toru Tanaka ◽  
Takehisa Shimizu ◽  
Hiroshi Doi ◽  
Norimichi Koitabashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Protein Kinase ◽  
Cardiac Myocytes ◽  
Natriuretic Peptide ◽  
Neonatal Rat ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Failing Heart ◽  
Epor Expression

Backgroud: Recent studies demonstrated non-hematopoietical effects of Erythropoietin (Epo) and its receptor (EpoR) in a variety of tissues including cardiovascular system. Epo treatment improves cardiac function in patients with heart failure and reduces infarct size after ischemia/reperfusion injury in the heart. However, little attention has been paid for the endogenous regulatory mechanisms regulating EpoR expression. In this study, we hypothesize that B-type natriuretic peptide upregulates EpoR gene expression in failing heart. Methods and Results: Wister rats underwent transverse aortic constriction surgery to induce hypertrophy. RT-PCR analyses of those rats showed that EpoR mRNA levels were increased in the left ventricle and positively correlated with the levels of BNP mRNA (n=10, r=0.67, p<0.05). Next we examined the expression of EpoR in human failing heart by using autopsy specimens and found that EpoR mRNA levels were significantly elevated in patients with dilated cardiomyopathy compared with those in normal heart. Immunohistochemistry of endomyocardial biopsy specimens of failing heart (n=54) showed that EpoR mRNA levels were correlated with severity of cardiac dysfunction estimated by diameter of cardiac chambers, pathomorphology, serum BNP concentration and functional class of New York Heart Association. Interestingly, stimulation of cultured neonatal rat cardiac myocytes with BNP, but not with hypertrophic reagents including endothelin I, angiotensin II and norepinephrine, significantly increased the EpoR mRNA levels in a time-dependent manner. Overexpression of cGMP-dependent protein kinase (PKG) increased EpoR transcript in cultured cardiac myocytes. BNP-induced EpoR expression was abrogated in the presence of KT5823, a specific inhibitor for PKG. Conclusion: These results suggest a role for BNP in mediating an induction of EpoR expression in failing myocardium and indicate that the cardiac EpoR gene is a target of cGMP/PKG signaling.

scholarly journals Bakuchiol protects against pathological cardiac hypertrophy by blocking NF-κB signaling pathway

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Zheng Wang ◽  
Lu Gao ◽  
Lili Xiao ◽  
Lingyao Kong ◽  
Huiting Shi ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Pressure Overload ◽  
Neonatal Rat ◽  
Oral Gavage ◽  
Aortic Banding ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy ◽  
First Time

Bakuchiol (Bak), a monoterpene phenol isolated from the seeds of Psoralea corylifolia, has been widely used to treat a large variety of diseases in both Indian and Chinese folkloric medicine. However, the effects of Bak on cardiac hypertrophy remain unclear. Therefore, the present study was designed to determine whether Bak could alleviate cardiac hypertrophy. Mice were subjected to aortic banding (AB) to induce cardiac hypertrophy model. Bak of 1 ml/100 g body weight was given by oral gavage once a day from 1 to 8 weeks after surgery. Our data demonstrated for the first time that Bak could attenuate pressure overload-induced cardiac hypertrophy and could attenuate fibrosis and the inflammatory response induced by AB. The results further revealed that the effect of Bak on cardiac hypertrophy was mediated by blocking the activation of the NF-κB signaling pathway. In vitro studies performed in neonatal rat cardiomyocytes further proved that the protective effect of Bak on cardiac hypertrophy is largely dependent on the NF-κB pathway. Based on our results, Bak shows profound potential for its application in the treatment of pathological cardiac hypertrophy, and we believe that Bak may be a promising therapeutic candidate to treat cardiac hypertrophy and heart failure.

scholarly journals MiR-26a-5p inhibits GSK3β expression and promotes cardiac hypertrophy in vitro

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10371
Author(s):  
Liqun Tang ◽  
Jianhong Xie ◽  
Xiaoqin Yu ◽  
Yangyang Zheng
Keyword(s):  
Cell Surface ◽  
Cardiac Hypertrophy ◽  
Surface Area ◽  
Myocardial Cell ◽  
Immunofluorescence Staining ◽  
Cell Surface Area ◽  
Direct Target

Background The role of miR-26a-5p expression in cardiac hypertrophy remains unclear. Herein, the effect of miR-26a-5p on cardiac hypertrophy was investigated using phenylephrine (PE)-induced cardiac hypertrophy in vitro and in a rat model of hypertension-induced hypertrophy in vivo. Methods The PE-induced cardiac hypertrophy models in vitro and vivo were established. To investigate the effect of miR-26a-5p activation on autophagy, the protein expression of autophagosome marker (LC3) and p62 was detected by western blot analysis. To explore the effect of miR-26a-5p activation on cardiac hypertrophy, the relative mRNA expression of cardiac hypertrophy related mark GSK3β was detected by qRT-PCR in vitro and vivo. In addition, immunofluorescence staining was used to detect cardiac hypertrophy related mark α-actinin. The cell surface area was measured by immunofluorescence staining. The direct target relationship between miR-26a-5p and GSK3β was confirmed by dual luciferase report. Results MiR-26a-5p was highly expressed in PE-induced cardiac hypertrophy. MiR-26a-5p promoted LC3II and decreased p62 expression in PE-induced cardiac hypertrophy in the presence or absence of lysosomal inhibitor. Furthermore, miR-26a-5p significantly inhibited GSK3β expression in vitro and in vivo. Dual luciferase report results confirmed that miR-26a-5p could directly target GSK3β. GSK3β overexpression significantly reversed the expression of cardiac hypertrophy-related markers including ANP, ACTA1 and MYH7. Immunofluorescence staining results demonstrated that miR-26a-5p promoted cardiac hypertrophy related protein α-actinin expression, and increased cell surface area in vitro and in vivo. Conclusion Our study revealed that miR-26a-5p promotes myocardial cell autophagy activation and cardiac hypertrophy by regulating GSK3β, which needs further research.

Differential Regulation of Ventricular Adrenomedullin and Atrial Natriuretic Peptide Gene Expression in Pressure and Volume Overload in the Rat

1998 ◽  
Vol 94 (4) ◽  
pp. 359-365 ◽  
Author(s):  
Michael Kaiser ◽  
Ole Kahr ◽  
Yasuyuki Shimada ◽  
Pamela Smith ◽  
Martin Kelly ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Atrial Natriuretic Peptide ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Mrna Level ◽  
Mrna Levels ◽  
Post Surgery ◽  
Infarction Heart ◽  
Atrial Natriuretic

1. Adrenomedullin is a recently discovered vasodilating and natriuretic peptide whose physiological and pathophysiological roles remain to be established. Like atrial natiuretic peptide adrenomedullin is expressed in the left ventricle. Ventricular expression of atrial natriuretic peptide is known to be markedly increased by volume or pressure overload. In this study we investigated whether ventricular expression of adrenomedullin is similarly stimulated under such conditions. 2. Ventricular adrenomedullin and atrial natriuretic peptide mRNA levels as well as those of a loading control mRNA (glyceraldehyde-3-phosphate dehydrogenase) were quantified by Northern blot analysis in (a) rats with severe post-infarction heart failure induced by left coronary ligation at 30 days post-surgery and (b) in rats with pressure-related cardiac hypertrophy induced by aortic banding at several time points (0.5, 1 and 4 h, and 1, 4, 7 and 28 days) after surgery. Levels were compared with those in matched sham-operated controls. 3. The mRNA level of atrial natriuretic peptide was markedly increased (8–10-fold) in the left ventricle of animals with post-infarction heart failure. In contrast, there was only a modest (40%) increase in the level of adrenomedullin mRNA. In rats with pressure-induced cardiac hypertrophy the ventricular level of atrial natriuretic peptide mRNA was again markedly increased (maximum 10-fold). The increase was first noticeable at 24 h post-banding and persisted until 28 days. In contrast, there was no change in adrenomedullin mRNA level compared with sham-operated rats at any time point. 4. Despite having similar systemic effects, the expression of adrenomedullin and atrial natriuretic peptide in the left ventricle is differently regulated. The findings imply distinct roles for the two peptides. The results do not support an important role for ventricular adrenomedullin expression in the remodelling process that occurs during the development of cardiac hypertrophy but suggest that ventricular adrenomedullin participates in the local and/or systemic response to heart failure

MicroRNA-183 as a Novel Regulator Protects Against Cardiomyocytes Hypertrophy via Targeting TIAM1

2020 ◽  
Author(s):  
Fu-han Gong ◽  
Xi-Lu Chen ◽  
Quan Zhang ◽  
Xiao-qiang Xiao ◽  
Yong-sheng Yang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Bioinformatics Analysis ◽  
Negative Control ◽  
Neonatal Rat ◽  
Luciferase Reporter ◽  
Ang Ii ◽  
Direct Target Gene ◽  
Phenotype Analysis ◽  
Reporter Assays

Abstract BACKGROUND MicroRNAs serve as important regulators of the pathogenesis of cardiac hypertrophy. Among them, miR-183 is well documented as a novel tumor suppressor in previous studies, whereas it exhibits a downregulated expression in cardiac hypertrophy recently. The present study was aimed to examine the effect of miR-183 on cardiomyocytes hypertrophy. METHODS Angiotensin II (Ang II) was used for establishment of cardiac hypertrophy model in vitro. Neonatal rat ventricular cardiomyocytes transfected with miR-183 mimic or negative control were further utilized for the phenotype analysis. Moreover, the bioinformatics analysis and luciferase reporter assays were used for exploring the potential target of miR-183 in cardiomyocytes. RESULTS We observed a significant decreased expression of miR-183 in hypertrophic cardiomyocytes. Overexpression of miR-183 significantly attenuated the cardiomyocytes size morphologically and prohypertrophic genes expression. Moreover, we demonstrated that TIAM1 was a direct target gene of miR-183 verified by bioinformatics analysis and luciferase reporter assays, which showed a decreased mRNA and protein expression in the cardiomyocytes transfected with miR-183 upon Ang II stimulation. Additionally, the downregulated TIAM1 expression was required for the attenuated effect of miR-183 on cardiomyocytes hypertrophy. CONCLUSIONS Taken together, these evidences indicated that miR-183 acted as a cardioprotective regulator for the development of cardiomyocytes hypertrophy via directly regulation of TIAM1.

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