scholarly journals lncRNA UCA1 Is a Novel Regulator in Cardiomyocyte Hypertrophy through Targeting the miR-184/HOXA9 Axis

2018 ◽  
Vol 8 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Gaoliang Zhou ◽  
Chao Li ◽  
Jun Feng ◽  
Jing Zhang ◽  
Yanyan Fang
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiac Hypertrophy ◽  
Cardiomyocyte Hypertrophy ◽  
Pcr Analysis ◽  
Biological Processes ◽  
Transverse Aortic Constriction ◽  
Spearman Correlation ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Direct Target

Cardiac hypertrophy is closely associated with a series of cardiovascular diseases, including heart failure and sudden death in particular. An in-depth comprehension of the pathogenesis of cardiac hypertrophy will improve the diagnosis and therapy of cardiac hypertrophy. It has been acknowledged that long noncoding RNAs/microRNAs (lncRNAs/miRNAs) are crucial regulators in diverse biological processes, including various cardiovascular diseases, in multiple manners. Nevertheless, the biological roles of lncRNA UCA1 and miR-184 in cardiac hypertrophy are scarcely reported. In this paper, qRT-PCR analysis exhibited that lncRNA UCA1 was highly expressed in mice heart treated with transverse aortic constriction (TAC) and the cardiomyocytes treated with phenylephrine (PE). On the contrary, miR-184 was downregulated under the same conditions. In addition, it was deduced that lncRNA UCA1 was reversely related with miR-184 in PE-triggered hypertrophic cardiomyocytes, confirmed by the Spearman correlation analysis. The knockdown of UCA1 or the overexpression of miR-184 lessened the enlarged surface area of cardiomyocytes and the elevated expressions of fetal genes (ANP and BNP) induced by PE. Later, it was determined that miR-184 was a direct target of UCA1, whereas the mRNA HOXA9 was a target of miR-184. Rescue assays indicated that UCA1 promoted the progression of cardiac hypertrophy through competitively binding with miR-184 to enhance the expression of HOXA9.

Microarray analysis of gene expression after transverse aortic constriction in mice

2004 ◽  
Vol 19 (1) ◽  
pp. 93-105 ◽  
Author(s):  
Mingming Zhao ◽  
Amy Chow ◽  
Jennifer Powers ◽  
Giovanni Fajardo ◽  
Daniel Bernstein
Keyword(s):  
Gene Expression ◽  
Statistical Analysis ◽  
Cardiac Hypertrophy ◽  
Heart Function ◽  
Expression Profiles ◽  
Alternative Methods ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Altered Expression ◽  
Qrt Pcr

Cardiac hypertrophy is a compensatory response initially beneficial to heart function but can ultimately lead to cardiac decompensation. It is an integrated process involving multiple cellular signaling pathways and their cross talk. Microarray GeneChip technology is a powerful new tool to identify gene expression profiles of cardiac hypertrophy. To identify well-characterized as well as novel adaptive mechanisms, we utilized a murine model of compensated pressure overload hypertrophy (transverse aortic constriction, TAC). At 48 h, 10 days, and 3 wk, hearts were harvested and total RNA hybridized to Affymetrix U74Av2 GeneChips, which contain a 12,488-gene/EST probe set. Verification of gene expression was performed by SYBR quantitative real-time RT-PCR (QRT-PCR) for selected genes. A rigorous evaluation of the adequacy of the control condition was also performed. For statistical analysis we generated a four-step filtering criteria. Our results show an upregulation of 38 genes (48 h), 269 genes (10 days), and 203 genes (3 wk) and downregulation of 15 genes (48 h), 160 genes (10 days), and 124 genes (3 wk). Transcripts differentially expressed after TAC were categorized into 12 functional groups and revealed the presence of several intriguing transcripts, e.g., cell proliferation-related Ki-67 and several apoptosis-related genes. Overall changes in QRT-PCR were in accordance with GeneChip data, with the highest correlation for genes with the largest up- or downregulation with TAC. Thus TAC results in altered expression of genes in several pathways regulating both cardiac structure and function. However, for in vivo gene microarray experiments, it is critical to define adequate controls, perform rigorous statistical analysis, and provide validation by alternative methods.

scholarly journals Leonurine Attenuates Pressure-Overload Cardiac Hypertrophy Induced By Abdominal Aortic Constriction In Rats

2021 ◽  
Author(s):  
Ding Xiaoli ◽  
Yuan Qingqing ◽  
Qian Haibing
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ang Ii ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Abdominal Aortic

Abstract Background: Myocardial hypertrophy occurs in many cardiovascular diseases. Leonurine (Leo) is commonly used for cardiovascular and cerebrovascular diseases. However, whether it can prevent cardiac hypertrophy is not known. The aim of this study was to investigate the effect and mechanism of Leonurine (Leo) against pressure-overload cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Methods: To answer this question, we prove it in the following way: Cardiac function was evaluated by hemodynamic; the left ventricle enlargement was measured by heart weight index (HWI) and left ventricular mass index (LVWI); myocardial tissue changes and myocardial cell diameter (MD) were determined by Hematoxylin and eosin (HE) staining; theβ-myosin heavy chain(β-MHC)and atrial natriuretic factor (ANF), which are recognized as a marker of cardiac hypertrophy, were determined by Real-time quantitative PCR (qRT-PCR), then another gene phospholipase C (PLC), inositol triphosphate (IP3), which associated with RAS were determined by Western blot(WB). angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R) were determined by ELISA, WB and qRT-PCR methods. Finally, we measured the level of Ca2+ by microplate method and the protooncogene c-fos and c-myc mRNA in left ventricular myocardium by qRT-PCR.Results: Compare with control group, Leonurine can improve systolic dysfunction; inhibit the increase of left cardiac; inhibit myocardial cells were abnormally large and restrain the changes of cardiac histopathology; decrease the expression of β-MHC, ANF, Ang II, AT1R, c-fos and c-myc mRNA and the protein levels of PLC, IP3, AngII and AT1R in left ventricular myocardium, in addition, the content of Ca2+ also decrease. Conclusion: Therefore, Leonurine can inhibit cardiac hypertrophy induced by AAC and its effects may be associated with RAS.

ANTAGONIZING THE CX3CR1 RECEPTOR MARKEDLY REDUCES DEVELOPMENT OF CARDIAC HYPERTROPHY AFTER TRANSVERSE AORTIC CONSTRICTION IN MICE

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Simona Nemska ◽  
Max Gassmann ◽  
Marie-Louise Bang ◽  
Nelly Frossard ◽  
Reza Tavakoli
Keyword(s):  
Cardiac Hypertrophy ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction

scholarly journals LCZ696, an Angiotensin Receptor-Neprilysin Inhibitor, Improves Cardiac Hypertrophy and Fibrosis and Cardiac Lymphatic Remodeling in Transverse Aortic Constriction Model Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Qing Ge ◽  
Li Zhao ◽  
Chen Liu ◽  
Xiaoming Ren ◽  
Yi-hui Yu ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Mouse Heart ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Expression Levels ◽  
Factor C ◽  
Proinflammatory Factors

Cardiac hypertrophy and ventricular remodeling following heart failure are important causes of high mortality in heart disease patients. The cardiac lymphatic system has been associated with limited research, but it plays an important role in the improvement of myocardial edema and the promotion of fluid balance. LCZ696 is a novel combination of angiotensin and neprilysin inhibitors. Here, we studied the role played by LCZ696 during transverse aortic constriction (TAC) induced cardiac hypertrophy and changes in the lymphatic system. Mice undergoing aortic coarctation were constructed to represent a cardiac hypertrophy model and then divided into random groups that either received treatment with LCZ696 (60 mg/kg/d) or no treatment. Cardiac ultrasonography was used to detect cardiac function, and hematoxylin and eosin (H&E) and Masson staining were used to detect myocardial hypertrophy and fibrosis. The proinflammatory factors interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were detected in the blood and heart tissues of mice. The protein expression levels of lymphatic-specific markers, such as vascular endothelial growth factor C (VEGF-C), VEGF receptor 3 (VEGFR3), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) were detected in mouse heart tissues. We also examined the colocalization of lymphatic vessels and macrophages by immunofluorescence. The results showed that LCZ696 significantly improved heart dysfunction, cardiac hypertrophy, and fibrosis and inhibited the expression of proinflammatory factors IL-6, IL-1β, and TNF-α in the circulating blood and heart tissues of mice. LCZ696 also decreased the protein expression levels of VEGF-C, VEGFR3, and LYVE-1 in mouse heart tissues, ameliorated the transport load of lymphatic vessels to macrophages, and improved the remodeling of the lymphatic system in the hypertrophic cardiomyopathy model induced by TAC.

scholarly journals Apocynum Tablet Protects against Cardiac Hypertrophy via Inhibiting AKT and ERK1/2 Phosphorylation after Pressure Overload

2014 ◽  
Vol 2014 ◽  
pp. 1-9
Author(s):  
Jianyong Qi ◽  
Qin Liu ◽  
Kaizheng Gong ◽  
Juan Yu ◽  
Lei Wang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Study Groups ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Cardioprotective Effects

Background. Cardiac hypertrophy occurs in many cardiovascular diseases. Apocynum tablet (AT), a traditional Chinese medicine, has been widely used in China to treat patients with hypertension. However, the underlying molecular mechanisms of AT on the hypertension-induced cardiac hypertrophy remain elusive. The current study evaluated the effect and mechanisms of AT on cardiac hypertrophy.Methods. We created a mouse model of cardiac hypertrophy by inducing pressure overload with surgery of transverse aortic constriction (TAC) and then explored the effect of AT on the development of cardiac hypertrophy using 46 mice in 4 study groups (combinations of AT and TAC). In addition, we evaluated the signaling pathway of phosphorylation of ERK1/2, AKT, and protein expression of GATA4 in the cardioprotective effects of AT using Western blot.Results. AT inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, Ser473 site of AKT, and protein expression of GATA4 and significantly inhibited cardiac hypertrophy and cardiac fibrosis at 2 weeks after TAC surgery (P<0.05).Conclusions. We experimentally demonstrated that AT inhibits cardiac hypertrophy via suppressing phosphorylation of ERK1/2 and AKT.

scholarly journals Modeling heart failure risk in diabetes and kidney disease: limitations and potential applications of transverse aortic constriction in high-fat-fed mice

2018 ◽  
Vol 314 (6) ◽  
pp. R858-R869 ◽  
Author(s):  
Wei Sheng Tan ◽  
Thomas P. Mullins ◽  
Melanie Flint ◽  
Sarah L. Walton ◽  
Helle Bielefeldt-Ohmann ◽  
...  
Keyword(s):  
Heart Failure ◽  
Kidney Disease ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Transverse Aortic Constriction ◽  
High Fat ◽  
Aortic Constriction ◽  
Failure Risk ◽  
Cardiovascular Prognosis ◽  
Fat Feeding

There is an increased incidence of heart failure in individuals with diabetes mellitus (DM). The coexistence of kidney disease in DM exacerbates the cardiovascular prognosis. Researchers have attempted to combine the critical features of heart failure, using transverse aortic constriction, with DM in mice, but variable findings have been reported. Furthermore, kidney outcomes have not been assessed in this setting; thus its utility as a model of heart failure in DM and kidney disease is unknown. We generated a mouse model of obesity, hyperglycemia, and mild kidney pathology by feeding male C57BL/6J mice a high-fat diet (HFD). Cardiac pressure overload was surgically induced using transverse aortic constriction (TAC). Normal diet (ND) and sham controls were included. Heart failure risk factors were evident at 8-wk post-TAC, including increased left ventricular mass (+49% in ND and +35% in HFD), cardiomyocyte hypertrophy (+40% in ND and +28% in HFD), and interstitial and perivascular fibrosis (Masson’s trichrome and picrosirius red positivity). High-fat feeding did not exacerbate the TAC-induced cardiac outcomes. At 11 wk post-TAC in a separate mouse cohort, echocardiography revealed reduced left ventricular size and increased left ventricular wall thickness, the latter being evident in ND mice only. Systolic function was preserved in the TAC mice and was similar between ND and HFD. Thus combined high-fat feeding and TAC in mice did not model the increased incidence of heart failure in DM patients. This model, however, may mimic the better cardiovascular prognosis seen in overweight and obese heart failure patients.

scholarly journals Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure

2017 ◽  
Vol 114 (45) ◽  
pp. 12033-12038 ◽  
Author(s):  
Iacopo Gesmundo ◽  
Michele Miragoli ◽  
Pierluigi Carullo ◽  
Letizia Trovato ◽  
Veronica Larcher ◽  
...  
Keyword(s):  
Heart Failure ◽  
Growth Hormone ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Therapeutic Potential ◽  
Growth Hormone Releasing Hormone ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction

It has been shown that growth hormone-releasing hormone (GHRH) reduces cardiomyocyte (CM) apoptosis, prevents ischemia/reperfusion injury, and improves cardiac function in ischemic rat hearts. However, it is still not known whether GHRH would be beneficial for life-threatening pathological conditions, like cardiac hypertrophy and heart failure (HF). Thus, we tested the myocardial therapeutic potential of GHRH stimulation in vitro and in vivo, using GHRH or its agonistic analog MR-409. We show that in vitro, GHRH(1-44)NH2 attenuates phenylephrine-induced hypertrophy in H9c2 cardiac cells, adult rat ventricular myocytes, and human induced pluripotent stem cell-derived CMs, decreasing expression of hypertrophic genes and regulating hypertrophic pathways. Underlying mechanisms included blockade of Gq signaling and its downstream components phospholipase Cβ, protein kinase Cε, calcineurin, and phospholamban. The receptor-dependent effects of GHRH also involved activation of Gαs and cAMP/PKA, and inhibition of increase in exchange protein directly activated by cAMP1 (Epac1). In vivo, MR-409 mitigated cardiac hypertrophy in mice subjected to transverse aortic constriction and improved cardiac function. Moreover, CMs isolated from transverse aortic constriction mice treated with MR-409 showed improved contractility and reversal of sarcolemmal structure. Overall, these results identify GHRH as an antihypertrophic regulator, underlying its therapeutic potential for HF, and suggest possible beneficial use of its analogs for treatment of pathological cardiac hypertrophy.

scholarly journals FABP3 Deficiency Exacerbates Metabolic Derangement in Cardiac Hypertrophy and Heart Failure via PPARα Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Lingfang Zhuang ◽  
Ye Mao ◽  
Zizhu Liu ◽  
Chenni Li ◽  
Qi Jin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cardiac Hypertrophy ◽  
Metabolic Reprogramming ◽  
Acid Oxidation ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Metabolic Derangement ◽  
Fatty Acid Binding ◽  
Atp Production ◽  
Incidence And Mortality

Background: Cardiac hypertrophy was accompanied by various cardiovascular diseases (CVDs), and due to the high global incidence and mortality of CVDs, it has become increasingly critical to characterize the pathogenesis of cardiac hypertrophy. We aimed to determine the metabolic roles of fatty acid binding protein 3 (FABP3) on transverse aortic constriction (TAC)-induced cardiac hypertrophy.Methods and Results: Transverse aortic constriction or Ang II treatment markedly upregulated Fabp3 expression. Notably, Fabp3 ablation aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction. Multi-omics analysis revealed that Fabp3-deficient hearts exhibited disrupted metabolic signatures characterized by increased glycolysis, toxic lipid accumulation, and compromised fatty acid oxidation and ATP production under hypertrophic stimuli. Mechanistically, FABP3 mediated metabolic reprogramming by directly interacting with PPARα, which prevented its degradation and synergistically modulated its transcriptional activity on Mlycd and Gck. Finally, treatment with the PPARα agonist, fenofibrate, rescued the pro-hypertrophic effects of Fabp3 deficiency.Conclusions: Collectively, these findings reveal the indispensable roles of the FABP3–PPARα axis on metabolic homeostasis and the development of hypertrophy, which sheds new light on the treatment of hypertrophy.

scholarly journals RNA Sequencing Reveals Novel LncRNAs/mRNAs Network Associated with Puerarin-mediated Inhibition of Cardiac Hypertrophy in Mice

2021 ◽  
Author(s):  
Shan Ye ◽  
Wei-Yang Chen ◽  
Caiwen Ou ◽  
Min-Sheng Chen
Keyword(s):  
Mouse Model ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Rna Sequencing ◽  
Expression Patterns ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Biological Processes ◽  
Rna Seq ◽  
Qrt Pcr

Abstract Background: Evidence has demonstrated that puerarin is a potential drug for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs in a cardiac hypertrophy mouse model after puerarin treatment.Methods: A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to systematically analyze global gene expression. The target lncRNAs were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression (CNC) network was established to find the interaction of lncRNAs and mRNAs. The molecular functions, biological processes, molecular components and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyto Encyclopedia of Genes and Genomes (KEGG) pathways analysis.Results: Puerarin exhibited obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC upregulated 19 lncRNAs and downregulated 18 lncRNAs, which could be revised by puerarin treatment (Fold change ≥ 3 and P< 0.05). Expression alterations of selected lncRNAs ENSMUST00000125726, ENSMUST00000143044 and ENSMUST00000212795 were confirmed by qRT-PCR. Pearson’s correlation coefficients of co-expression levels suggested that there was interactive relationship between those 3 validated altered lncRNAs and 5,500 mRNAs (r > 0.95 or r < −0.95). Those co-expressed mRNAs were enriched in some important biological processes such as vesicle-mediated transport, sin 3 complex, and translation initiation factor activity. KEGG analyses suggested that those lncRNA-interacted mRNAs were enriched in RNA transport, ribosome biogenesis in eukaryotes and proteasome signaling pathway. Conclusion: Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the ENSMUST00000125726 /ENSMUST00000143044 / ENSMUST00000212795 -mRNAs network.

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