scholarly journals The role of dye affinity in optical measurements of Cai2+ transients in cardiac muscle

2014 ◽  
Vol 307 (1) ◽  
pp. H73-H79 ◽  
Author(s):  
Wei Kong ◽  
Vladimir G. Fast
Keyword(s):  
Optical Fibers ◽  
Cardiac Tissue ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Optical Measurements ◽  
Neonatal Rat ◽  
High Affinity ◽  
Cycle Lengths ◽  
Rat Myocytes

Previous experiments in cultures of neonatal rat myocytes demonstrated that the shape of Cai2+ transients measured using high-affinity Ca2+-sensitive dyes may be misrepresented. The purpose of this study was to examine the role of dye affinity in Cai2+ measurements in intact adult cardiac tissue by comparing optical recordings obtained with high- and low-affinity dyes. Experiments were carried out in porcine left ventricular (LV) wedge preparations stained locally by intramural injection via microcapillaries (diameter = 150 μm) with a low-affinity Ca2+-sensitive dye Fluo-4FF or Fluo-2LA (nominal Kd, ∼7–10 μmol/l), high-affinity dye Rhod-2 ( Kd = 0.57 μmol/l), and Fluo-4 or Fluo-2MA ( Kd, ∼0.4 μmol/l); in addition, tissue was stained with transmembrane potential ( Vm)-sensitive dye RH-237. Optical recordings of Vm and Cai2+ were made using optical fibers (diameter = 325 μm) glued with the microcapillaries. The durations of Cai2+ transients measured at 50% level of recovery (CaD50) using high-affinity Fluo-4/Fluo-2MA dyes were up to ∼81% longer than those measured with low-affinity Fluo-4FF/Fluo-2LA at long pacing cycle lengths (CL). In Fluo-4/Fluo-2MA measurements at long CLs, Cai2+ transients often (∼50% of cases) exhibited slow upstroke rise and extended plateau. In Rhod-2 measurements, CaD50 was moderately longer (up to ∼35%) than in Fluo-4FF recordings, but Cai2+ transient shapes were similar. In all series of measurements, mean action potential duration values were not significantly different ( P > 0.05). The delays between Vm and Cai2+ upstrokes were comparable for low- and high-affinity dyes ( P > 0.05). In conclusion, measurements of Cai2+ transient in ventricular myocardium are strongly affected by the affinity of Ca2+ dyes. The high-affinity dyes may overestimate the duration and alter the shape of Cai2+ transients.

Abstract 16383: Inhibition of Egfr Signalling Promotes Maladaptive Cardiac Remodelling in Hypertensive Heart Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Susanna Cooper ◽  
Zoe Haines ◽  
Viridiana Alcantara Alonso ◽  
Joshua J Cull ◽  
Feroz Ahmad ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mrna Expression ◽  
Left Ventricular ◽  
Egfr Inhibitors ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Rat Cardiomyocytes ◽  
Egfr Ligands ◽  
Cardiac Adaptation

Introduction: Epidermal growth factor (EGF) receptors (EGFRs: ERBB1-4) are activated by a family of ligands (e.g. EGF, Hb-EGF, EREG, TGFa), signaling through ERK1/2 and Akt to promote cell division and cancer. Antibody-based inhibition of ERBB2 in breast cancer can cause heart failure, but the role of other receptors and EGFR ligands in the heart, and potential cardiotoxicity of generic EGFR inhibitors is unclear. Hypothesis: We hypothesize that EGFR ligands play an important role in cardiac adaptation to hypertension, acting through EGFRs to promote adaptive remodelling. Methods & Results: EGF ligand/receptor mRNA expression was assessed in human failing hearts and normal controls (n=12/8). EGFRs were expressed at similar levels, but ligand expression differed with significant up- or downregulation of EGF/Hb-EGF vs EREG/TGFa, respectively, in failing hearts (p<0.05). EGF potently activated ERK1/2 and Akt (assessed by immunoblotting) in neonatal rat cardiomyocytes, leading to hypertrophy (p<0.05, n=4). The anti-cancer drug afatinib inhibits EGFRs. To assess the role of EGF signaling in cardiac adaptation to hypertension in vivo , C57Bl/6J mice (n=6) were treated with 0.8 mg/kg/d angiotensin II (AngII; 7d) ± 0.45 mg/kg/d afatinib. AngII promoted cardiac hypertrophy with increased left ventricular (LV) wall thickness (WT) and decreased LV internal diameter (ID; assessed by echocardiography). Afatinib enhanced AngII-induced hypertrophy with significantly increased WT:ID ratios (1.30-fold and 1.54-fold in diastole and systole, respectively; p<0.05) but inhibited AngII-induced increases in Nppb mRNA expression and cardiomyocyte cross-sectional area (208.80±9.78 vs 161.10±3.87μm 2 ; p<0.05). In contrast, Col1a1 mRNA expression was enhanced by afatinib, along with interstitial and perivascular fibrosis (3.21±0.38 vs 5.61±0.46, 0.98±0.06 vs 1.45±0.18 % area; p<0.05). Conclusion: EGFR signaling is modulated in human heart failure, promotes cardiomyocyte hypertrophy and is required for cardiac adaptation to hypertension. Since EGFR inhibition in hypertension prevents adaptive cardiomyocyte hypertrophy whilst promoting fibrosis, EGFR inhibitors are likely to cause cardiac dysfunction and be cardiotoxic in hypertensive patients.

scholarly journals Transient Upregulation of Protein Kinase C in Pressure-Overloaded Neonatal Rat Myocardium

2010 ◽  
pp. 25-33 ◽  
Author(s):  
B Hamplová ◽  
F Novák ◽  
F Kolář
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Left Ventricular Myocardium ◽  
Aortic Constriction ◽  
Cardiac Growth ◽  
Kinase C

Protein kinase C (PKC) appears to play a significant role in the signal transduction of cardiac growth and development. The aim of this study was to determine changes in the total PKC activity and the expression of PKC isoforms α, δ and ε in the rat heart that was affected by pressure overload imposed at postnatal day (d) 2. Three groups of Wistar rats were employed for the experiment: rats submitted to the abdominal aortic constriction (AC), sham-operated controls (SO) and intact controls. Animals were sacrificed at d2, d3, d5 and d10. The total PKC activity was measured by the incorporation of 32P into histone IIIS and the expression of PKC was analyzed by immunoblotting in the homogenate of the left ventricular myocardium and in the cytosolic, membrane-enriched (105 × g) and nuclear-cytoskeletalmyofilament-enriched (103 × g) fractions. We observed the significant transient increase in both the total PKC activity and the expression of all isoforms at d5 (the 3rd day after the operation) in the cardiac homogenate of AC rats as compared with SO animals. Aortic constriction did not significantly affect the distribution of activity and isoform abundance among individual cellular fractions except for PKCδ, which increased significantly at d10 in the cytosolic fraction at the expense of the membraneenriched fraction. It is concluded that PKCα, PKCδ and PKCε undergo transient upregulation associated with the accelerated cardiac growth induced by pressure overload imposed in the very early postnatal period.

Functional role of myocardial electrical remodeling in diabetic rabbits

2015 ◽  
Vol 93 (4) ◽  
pp. 245-252 ◽  
Author(s):  
Alexey O. Ovechkin ◽  
Marina A. Vaykshnorayte ◽  
Ksenia Sedova ◽  
Konstantin V. Shumikhin ◽  
Natalia V. Arteyeva ◽  
...  
Keyword(s):  
Left Ventricular Pressure ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Electrical Remodeling ◽  
Arrhythmogenic Substrate ◽  
Cardiac Pump Function ◽  
Hemodynamic Impairment ◽  
Diabetic Rabbits ◽  
Left Ventricular Base

The objective of the study was to investigate the role of electrical remodeling of the ventricular myocardium in hemodynamic impairment and the development of arrhythmogenic substrate. Experiments were conducted with 11 healthy and 12 diabetic (alloxan model, 4 weeks) rabbits. Left ventricular pressure was monitored and unipolar electrograms were recorded from 64 epicardial leads. Aortic banding was used to provoke arrhythmia. The diabetic rabbits had prolonged QTc, with activation–recovery intervals (surrogates for repolarization durations) being relatively short on the left ventricular base and long on the anterior apical portions of both ventricles (P < 0.05). In the diabetic rabbits, a negative correlation (–0.726 to –0.817) was observed between dP/dtmax, dP/dtmin, and repolarization dispersions. Under conditions of systolic overload (5 min), tachyarrhythmias were equally rare and the QTc and activation–recovery intervals were shortened in both groups (P < 0.05), whereas QRS was prolonged in the diabetic rabbits only. The repolarization shortening was more pronounced on the apex, which led to the development of apicobasal and interventricular end of repolarization gradients in the healthy animals, and to the flattening of the repolarization profile in the diabetic group. Thus, the diabetes-related pattern of ventricular repolarization was associated with inotropic and lusitropic impairment of the cardiac pump function.

P6283Downregulation of Tim44 exacerbates oxidative stress-induced ROS production and cardiomyocytes death by reducing mitochondrial SOD2

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Ikeda ◽  
S Matsushima ◽  
K Okabe ◽  
A Ishikita ◽  
T Tadokoro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Remodeling ◽  
Protein Import ◽  
Mitochondrial Fraction ◽  
Left Ventricular ◽  
Protein Carbonylation ◽  
Neonatal Rat ◽  
Ros Production ◽  
Protein Levels

Abstract Background Mitochondrial dysfunction has been highlighted as a critical driver of cardiac remodeling and failure. Mitochondria contains about 1500 proteins, 99% of which are encoded in the nuclear genome. Therefore, protein import into mitochondria is essential to maintain mitochondrial function. Previous reports suggest that nuclear-encoded mitochondrial precursor proteins import into mitochondria by multiple complex; translocase of outer membrane (TOM), translocase of inner membrane (TIM), and protein associated motor (PAM). However, the role of these protein import machineries of mitochondria in cardiac remodeling remains to be elucidated. Objective The purpose of this study was to elucidate the role of TOM, TIM, and PAM complex in cardiac remodeling and cardiomyocyte death. Methods and results C57BL/6J mice were subjected to myocardial infarction (MI) by permanent ligation of left anterior descending artery. Four weeks after operation, MI-mice demonstrated left ventricular (LV) dilation (LV end-diastolic dimension: 3.91 vs. 5.54 mm, n=8–11, p<0.05) and dysfunction (LV fractional shortening: 33.3 vs. 7.7%, n=8–11, p<0.05). Tim44 protein levels, a component of PAM complex, in mitochondrial fraction from non-infarcted left ventricle were significantly decreased compared with those in the heart from sham-operated mice by 39% (p<0.05), whereas other proteins related to TOM, TIM and PAM complex such as Tom20, Tom22, Tom40, Tom70, Tim22, Tim23 and mtHSP70 were not altered between MI-mice and sham-mice. In addition, blue-native polyacrylamide gel electrophoresis revealed that a protein complex associated to Tim44 was significantly decreased in non-infarcted LV by 40% (p<0.05). Superoxide dismutase 2 (SOD2), a mitochondrial matrix protein, was decreased in mitochondrial fraction from non-infarcted LV by 20% (p<0.05), accompanied by enhancing protein carbonylation, a marker of oxidative stress, by 40% (p<0.05). To assess the role of Tim44, it was downregulated by small interfering RNA in cultured neonatal rat ventricular myocytes (NRVMs). Knockdown of Tim44 significantly decreased SOD2 protein levels in mitochondrial fractionation (22%, p<0.05), with no significant changes in its mRNA levels. Furthermore, knockdown of Tim44 significantly increased protein carbonylation (20%, p<0.05) and cleaved caspase 3 (47%, p<0.05) and decreased cell viability (69%, p<0.05), assessed by cell titer assay, in H2O2-treatred NRVMs. Conclusions Downregulation of Tim44 exacerbates oxidative stress-induced ROS production and cardiomyocytes death, which is associated with a decrease in mitochondrial SOD2. Endogenous Tim44 might play a protective role in cardiac remodeling by attenuating oxidative stress and cardiomyocyte death via SOD2 import into mitochondria.

P6292Role of CXCL12gamma isoform and its interactions with heparan-sulfates in post-ischemic cardiac remodeling

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Duval ◽  
I Zlatanova ◽  
Y Sun ◽  
P Alayrac ◽  
I Gomez ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Cardiac Tissue ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Vascular Growth ◽  
Heparan Sulfates

Abstract Introduction Myocardial infarction (MI) is a severe ischemic disease precipitating long-term adverse remodeling and heart failure. The chemokine CXCL12/SDF-1 is essential for cardiovascular system development and plays a prominent role in physio-pathological processes such as inflammation, angiogenesis and tissue fibrosis. In addition to the binding to its cognate receptors CXCR4 and CXCR7, CXCL12 interacts with heparan-sulfates (HS) which coordinate its biological activity. We have previously highlighted the essential role of CXCL12/HS interactions in vascular growth and remodeling in the setting of critical limb ischemia. In addition, studies in experimental model of MI revealed a protective role for the CXCL12α isoform, through the regulation of cardiomyocyte survival and recruitment of inflammatory cells. However, in mice, three CXCL12 isoforms (α, β and γ) have been identified and, among them, the CXCL12γ isoform shows an unchallenged ability to cooperate with HS, suggesting a putative pivotal role in tissue repair. Objectives The aim of the study is to analyze the role of CXCL12γ isoform and the importance of CXCL12/HS interactions in post-ischemic cardiac remodeling in an acute model of MI. Methods MI was induced by permanent ligation of the left ascending coronary artery in mice carrying a Cxcl12 gene mutation that precludes interactions with HS (Cxcl12Gagtm) and in Cxcl12γ knock-in animals (Cxcl12γ-KI) harboring CXCL12γ deficiency. Alternatively, the impact of CXCL12γ overexpression and the importance of its interactions with HS was also evaluated in wild-type (WT) mice receiving transcutaneous echo-guided injections of adenovirus encoding WT Cxcl12γ or HS-binding-disabled Cxcl12γ in cardiac tissue. Cardiac function and remodeling have been assessed through echocardiography analysis, evaluation of infarct size, interstitial fibrosis, vascular growth (capillary and arteriole densities) and inflammatory cell infiltration into the cardiac tissue. Results After MI, Cxcl12Gagtm and Cxcl12γ-KI animals exhibit reduction in cardiac function and adverse left ventricular remodeling when compared to their respective WT littermates. Interestingly, overexpression of CXCL12γ in WT mice cardiac restored cardiac function by reducing the size of the infarcted area, interstitial fibrosis and promoting vascular growth. In sharp contrast, HS–binding disabled CXCL12gamma mutants failed to improve cardiac function and to abrogate adverse left ventricular remodeling. Conclusion We show that CXCL12γ isoform plays an important role in the regulation of post-ischemic cardiac function and remodeling and that its interactions with HS are essential for adequate cardiac repair in the setting of acute MI.

scholarly journals Secreted Frizzled-Related Protein 5 Protects Against Cardiac Rupture and Improves Cardiac Function Through Inhibiting Mitochondrial Dysfunction

2021 ◽  
Vol 8 ◽  
Author(s):  
Xin Huang ◽  
Yan Yan ◽  
Wen Zheng ◽  
Youcai Ma ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Ischemic Injury ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Cardiac Rupture ◽  
Left Ventricular Ejection ◽  
Heart Weight ◽  
Related Protein ◽  
Ampk Activity

Background: Secreted frizzled-related protein 5 (Sfrp5) has been suggested to be a protective regulatory protein in coronary heart disease. However, the role of Sfrp5 in regulating ischemic injury and its consequences is not known. The aim of our study was to explore the effects of Sfrp5 on hearts after myocardial infarction (MI) and to investigate the underlying mechanisms.Methods and Results: We found that Sfrp5 was downregulated over time in the heart tissue of MI mice. To further elucidate the role of Sfrp5 during MI, we established a cardiac overexpression of an Sfrp5 mouse model using the cardiotropic adeno-associated virus serotype 9 (AAV9). Overexpression of Sfrp5 significantly reduced infarct size as demonstrated by a decrease in mortality owing to cardiac rupture. Moreover, cardiac overexpression of Sfrp5 increased left ventricular function and mitochondrial biogenesis, decreased cardiomyocyte apoptosis, suppressed inflammation reaction, inhibited oxidative stress, and ameliorated cardiac remodeling as demonstrated by left ventricular ejection fraction, mitochondrial morphology, heart weight, NADH oxidase activity levels, and myocardial fibrosis at 2 weeks post-MI. At the molecular level, overexpression of Sfrp5 significantly increased the expression of p-AMPKThr172 protein with higher expression of mitochondrial fusion protein (MFN1 and MFN2) and lower expression of mitochondrial fission protein (p-Drp1Ser616/Mid49/MFF/Fis-1). In isolated neonatal rat cardiac myocytes, Sfrp5 treatment attenuated hypoxia-induced mitochondrial dysfunction. Inhibition of AMPK activity with compound C abrogated this benefit.Conclusions: Sfrp5 overexpression inhibits ischemic injury, reduces risk of cardiac rupture, ameliorates post-MI remodeling, and decreases the progression to heart failure via disrupting mitochondrial dysfunction and partly through normalizing the AMPK activity.

scholarly journals Role of Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Cardiac Tissue and Improvement of Cardiac Function: a Narrative Review

2020 ◽  
Vol 11 (1) ◽  
pp. 8446-8456
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Trichostatin A ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Point Of View

Recent efforts have made in order to novel therapeutic approaches to reduce the heavy cardiovascular burden. The use of cell therapy and applying stem cell-based therapies has received much attention; of particular interest are adipose-derived mesenchymal stem cells (ADSCs). The present review aimed to review the studies which examined and researched various aspects of ADSCs to improve cardiac function. A comprehensive review of all articles assessed and discussed the application of ADSCs in the improvement of cardiac tissue renewing and cardiomyocytes regeneration was planned and conducted by the two reviewers. The initial literature search revealed a total of 153 articles that, of those, 34 were considered eligible. From the perspective of heart tissue regeneration, the inductive role of ADSCs in sensing mechanical stimulation and produce collagen and elastin scaffolds, vascularizing cardiac tissue, and exosomes (vesicles derived from ADSCs) in ADSCs‐mediated myocardial protection has indicated. In the process of ADSCs differentiation to cardiomyocyte- like cells, the role of various targeted pathways have been identified that can be influenced by different elements such as TGF-beta1, phorbol myristate acetate, Angiotensin II, Rho-associated kinases, 5-Azaytidine, Sodium valproate, fibrin scaffold and trichostatin A have been highlighted. In the final, from a therapeutic point of view, the effectiveness of ADMSCs differentiation to cardiomyocytes as improving left ventricular functional state has been discussed. Summarizing the studies confirms a significant improvement in cardiac function following direct application of ADSCs or their transformation to cardiomyocytes by stimulating or inhibiting various cellular pathways leading reducing oxidative stress and inflammatory bed, reducing cardiomyocyte apoptosis, attenuating cardiac fibrosis, reducing the infiltration of immune cells and collagen deposition, and enhancing angiogenesis.

Abstract 172: Interleukin-10-mediated Activation of AKT and Bcl2 Inhibits Chronic Angiotensin II-induced Pathological Autophagy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Suresh K Verma ◽  
Prasanna Krishnamurthy ◽  
Venkata N Girikipathi ◽  
Tatiana Abramova ◽  
Moshin Khan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Pressure Overload ◽  
Interleukin 10 ◽  
Left Ventricular ◽  
Beclin 1 ◽  
Neonatal Rat ◽  
Physical Interaction ◽  
Ang Ii

Rationale: Although, autophagy is an essential cellular salvage process to maintain cellular homeostasis, pathological (stress-induced exaggerated/defective) autophagy can lead to cardiac abnormalities and ultimately heart failure. Therefore, a tight regulation of autophagic process would be important to treat chronic heart failure. Previously, we have shown that IL-10 strongly inhibited pressure overload-induced hypertrophy and heart failure, but role of IL-10 in regulation of pathological autophagy is not known. Hypothesis: We tested the hypothesis that IL-10 inhibits angiotensin II-induced pathological autophagy and this process, in part, led to improved cardiac function. Methods and Results: Pathological autophagy was induced in wild type (WT) and IL10-knockout (IL-10 KO) mice by angiotensin II (Ang II for 28 days) infusion. Ang II-induced left ventricular (LV) dysfunction and hypertrophic remodeling were accentuated in IL-10 KO mice compared to WT mice. IL-10 KO mice showed exaggerated autophagy as observed by Electron Microscopy and Western blotting (beclin 1, LC3 II/I and CHOP) with reduced AKT phosphorylation at serine-473. In neonatal rat ventricular cardiomyocytes (NRCM), Ang II treatment enhanced beclin1, LC3 and CHOP protein levels and inhibited AKT and 4EBP1 phosphorylation and Bcl2 levels. Interestingly, IL-10 inhibited Ang II-induced autophagic marker proteins. Additionally, IL-10 restored Ang II-induced suppression of AKT and 4EBP1 phosphrylation and restoration of Bcl2 protein level. Pharmacological inhibition of AKT via PI3K inhibitor (LY290002), reversed IL-10 responses on the Ang II-induced pathological autophagy, confirming that IL-10 mediated inhibition of autophagy is AKT dependent. Finally, as physical interaction of Bcl2 with beclin 1 is important to inhibit autophagy, we performed immunoprecipitation pull-down experiments, which showed Ang II disrupts the physical interaction of beclin 1 with Bcl2 and IL-10 reestablished this physical interaction to reduce autophagy. Conclusion: Our data provides a novel role of IL-10 in regulation of pathological autophagy and thus can act as a potential therapeutic molecule in treatment of chronic heart disease.

scholarly journals miR-139-5p inhibits isoproterenol-induced cardiac hypertrophy by targetting c-Jun

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Su Ming ◽  
Wang Shui-yun ◽  
Qiu Wei ◽  
Li Jian-hui ◽  
Hui Ru-tai ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Monogenic Disease ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Rat Cardiomyocytes ◽  
Neonatal Rat Cardiomyocytes ◽  
Regulatory Effects

Hypertrophic cardiomyopathy (HCM) is a serious monogenic disease characterized by cardiac hypertrophy, fibrosis, sudden cardiac death, and heart failure. Previously, we identified that miR-139-5p was down-regulated in HCM patients. However, the regulatory effects of miR-139-5p remain unclear. Thus, we investigated the role of miR-139-5p in the regulation of cardiac hypertrophy. The expression of miR-139-5p in left ventricular tissues in HCM patients and mice subjected to transverse aortic constriction (TAC) was significantly down-regulated. Knockdown of miR-139-5p expression in neonatal rat cardiomyocytes (NRCMs) induced cardiomyocyte enlargement and increased atrial natriuretic polypeptide (ANP) expression. Overexpression of miR-139-5p antagonized isoproterenol (ISO)-induced cardiomyocyte enlargement and ANP/brain natriuretic peptide (BNP) up-regulation. More importantly, we found that c-Jun expression was inhibited by miR-139-5p in NRCMs. Knockdown of c-Jun expression significantly attenuated cardiac hypertrophy induced by miR-139-5p deprivation. Our data indicated that miR-139-5p was down-regulated in the hearts of HCM patients and that it inhibited cardiac hypertrophy by targetting c-Jun expression.

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