scholarly journals Wogonin Inhibits Cardiac Hypertrophy by Activating Nrf-2-Mediated Antioxidant Responses

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xiaowen Shi ◽  
Bin Zhang ◽  
Zhenliang Chu ◽  
Bingjiang Han ◽  
Xueping Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Hypertrophy ◽  
Antioxidant Properties ◽  
Protein Detection ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
In Vivo Model ◽  
Pathophysiological Mechanism ◽  
H9c2 Cells ◽  
Rat Cardiomyocytes

Background. Cardiac hypertrophy is one of the initial disorders of the cardiovascular system and can induce heart failure. Oxidative stress is an important pathophysiological mechanism of cardiac hypertrophy. Wogonin (Wog), an important flavonoid derived from the root of Scutellaria baicalensis Georgi, is known to possess antioxidant properties. Methods. An in vitro model of cardiac hypertrophy was established by stimulating H9C2 cells and neonatal rat cardiomyocytes (NRCMs) with angiotensin II (AngII). The indices related to myocardial hypertrophy and oxidative stress were detected. An in vivo model of cardiac hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6 mice. Cardiac function was monitored by chest echocardiography, and the hypertrophy index was measured. The mice were then sacrificed for histological assays, with mRNA and protein detection. To further explore the role of nuclear factor- (erythroid-derived 2-) like 2 (Nrf-2) in regulating the antioxidant effects of Wog in cardiac hypertrophy, siRNA analysis was conducted. Results. Our results showed that Wog significantly ameliorated AngII-induced cardiomyocyte hypertrophy by inhibiting oxidative stress in H9C2 cells and NRCMs. In addition, Wog treatment prevented oxidative stress and improved cardiac hypertrophy in mice that underwent TAC. Using gene-specific siRNA for Nrf-2, we discovered that these antioxidative effects of Wog are mediated through Nrf-2 induction. Conclusions. Our results provide further evidence for the potential use of Wog as an antioxidative agent for treatment of cardiac hypertrophy, and Nrf-2 might serve as a therapeutic target in the treatment of cardiac hypertrophy.

scholarly journals LCZ696 Ameliorates Oxidative Stress and Pressure Overload-Induced Pathological Cardiac Remodeling by Regulating the Sirt3/MnSOD Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Shi Peng ◽  
Xiao-feng Lu ◽  
Yi-ding Qi ◽  
Jing Li ◽  
Juan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy

Aims. We aimed to investigate whether LCZ696 protects against pathological cardiac hypertrophy by regulating the Sirt3/MnSOD pathway. Methods. In vivo, we established a transverse aortic constriction animal model to establish pressure overload-induced heart failure. Subsequently, the mice were given LCZ696 by oral gavage for 4 weeks. After that, the mice underwent transthoracic echocardiography before they were sacrificed. In vitro, we introduced phenylephrine to prime neonatal rat cardiomyocytes and small-interfering RNA to knock down Sirt3 expression. Results. Pathological hypertrophic stimuli caused cardiac hypertrophy and fibrosis and reduced the expression levels of Sirt3 and MnSOD. LCZ696 alleviated the accumulation of oxidative reactive oxygen species (ROS) and cardiomyocyte apoptosis. Furthermore, Sirt3 deficiency abolished the protective effect of LCZ696 on cardiomyocyte hypertrophy, indicating that LCZ696 induced the upregulation of MnSOD and phosphorylation of AMPK through a Sirt3-dependent pathway. Conclusions. LCZ696 may mitigate myocardium oxidative stress and apoptosis in pressure overload-induced heart failure by regulating the Sirt3/MnSOD pathway.

Abstract 182: CTRP9 - A Novel Cardiac Derived Secreted Factor With Anti-hypertrophic Properties

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Astrid H Breitbart ◽  
Florian Brandes ◽  
Oliver Müller ◽  
Natali Froese ◽  
Mortimer Korf-Klingebiel ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Real Time ◽  
Real Time Pcr ◽  
Weight Ratio ◽  
Neonatal Rat ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Quantitative Real Time Pcr ◽  
Rat Cardiomyocytes ◽  
Knock Out

Background: CTRP9 (also called C1qtnf9) is a newly discovered secreted protein and a paralog of adiponectin. The biological functions of CTRP9, however, are still largely unknown. Results: Although previous data from a semi-quantitative real-time PCR had suggested that CTRP9 is mainly secreted by adipose tissue, we found its mRNA to be predominantly expressed in the heart by quantitative real-time PCR. Interestingly, we identified CTRP9 mRNA as significantly upregulated in hypertrophied mouse hearts (after 2 weeks of aortic constriction, TAC) as well as in hypertrophied human hearts (24±4-fold versus healthy human myocardium; p<0.01). LacZ staining in myocardial sections of C1qtnf9 tm1(KOMP)Vlcg mice (knock-out for CTRP9, containing a lacZ cassette to replace exon 1-3 of the gene) revealed exclusive expression of CTRP9 in capillary and venous endothelial cells. Adenoviral overexpression of CTRP9 or recombinant CTRP9 strongly inhibited cardiomyocyte hypertrophy (assessed as cell size, protein/DNA-ratio, expression of skeletal α-actin) after stimulation with phenylephrine (PE). Accordingly, myocardial overexpression of CTRP9 via a cardioselective adeno-associated virus (AAV9-CTRP9) in mice dramatically reduced cardiac hypertrophy after two weeks of pressure overload (heart weight/body weight ratio, HW/BW in mg/g: AAV9-control 6.5±0.2 versus AAV9-CTRP9 5.6±0.2; p<0.01). In turn, downregulation of CTRP9 by a specific siRNA aggravated cardiomyocyte growth in response to PE in vitro and CTRP9 knock-out (KO) mice exerted an enhanced hypertrophic response after two weeks of TAC in vivo (% increase in HW/BW versus sham: wild-type 77±13, KO 106±9; p<0.05). Mechanistically, we found that CTRP9 binds to the adiponectin receptor 1 (AdipoR1) and inhibits prohypertrophic mTOR signalling in cardiac myocytes. SiRNA mediated downregulation of AdipoR1 or mTOR in neonatal rat cardiomyocytes abolished the anti-hypertrophic effect of CTRP9. Conclusion: Endothelial cell derived CTRP9 inhibits cardiac hypertrophy through binding to AdipoR1 and inhibition of the mTOR pathway in cardiomyocytes. Therefore, myocardial application of CTRP9 could be a novel strategy to combat pathological cardiac hypertrophy.

scholarly journals Sinapic Acid Inhibits Cardiac Hypertrophy via Activation of Mitochondrial Sirt3/SOD2 Signaling in Neonatal Rat Cardiomyocytes

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1163
Author(s):  
Ui Jeong Yun ◽  
Dong Kwon Yang
Keyword(s):  
Cardiac Hypertrophy ◽  
Antioxidant Properties ◽  
Sinapic Acid ◽  
Pharmacological Action ◽  
Mitogen Activated Protein Kinase ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Neonatal Rat Cardiomyocytes ◽  
Mitochondrial Functions ◽  
Wide Range

Sinapic acid (SA) is a naturally occurring phenolic compound with antioxidant properties. It also has a wide range of pharmacological properties, such as anti-inflammatory, anticancer, and hepatoprotective properties. The present study aimed to evaluate the potential pharmacological effects of SA against hypertrophic responses in neonatal rat cardiomyocytes. In order to evaluate the preventive effect of SA on cardiac hypertrophy, phenylephrine (PE)-induced hypertrophic cardiomyocytes were treated with subcytotoxic concentrations of SA. SA effectively suppressed hypertrophic responses, such as cell size enlargement, sarcomeric rearrangement, and fetal gene re-expression. In addition, SA significantly inhibited the expression of mitogen-activated protein kinase (MAPK) proteins as pro-hypertrophic factors and protected the mitochondrial functions from hypertrophic stimuli. Notably, SA activated Sirt3, a mitochondrial deacetylase, and SOD2, a mitochondrial antioxidant, in hypertrophic cardiomyocytes. SA also inhibited oxidative stress in hypertrophic cardiomyocytes. However, the protective effect of SA was significantly reduced in Sirt3-silenced hypertrophic cardiomyocytes, indicating that SA exerts its beneficial effect through Sirt3/SOD signaling. In summary, this is the first study to reveal the potential pharmacological action and inhibitory mechanism of SA as an antioxidant against cardiac hypertrophy, suggesting that SA could be utilized for the treatment of cardiac hypertrophy.

scholarly journals Sophoricoside ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Maomao Gao ◽  
Fengjiao Hu ◽  
Manli Hu ◽  
Yufeng Hu ◽  
Hongjie Shi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Fibrosis ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Dependent Manner ◽  
Protective Effects ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy ◽  
Compound C

Abstract Aim: The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, the potential and significance of Sop should be broadened and it should be considered as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure. Methods: Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) enlargement model, the potent protection of Sop against cardiomyocytes enlargement was evaluated. The function of Sop was validated in mice received transverse aortic coarctation (TAC) or sham surgery. At 1 week after TAC surgery, mice were treated with Sop for the following 4 weeks, the hearts were harvested after echocardiography examination. Results: Our study revealed that Sop significantly mitigated TAC-induced heart dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, Sop treatment induced a remarkable activation of AMPK/mTORC1-autophagy cascade following sustained hypertrophic stimulation. Importantly, the protective effect of Sop was largely abolished by the AMPKα inhibitor Compound C, suggesting an AMPK activation-dependent manner of Sop function on suppressing pathological cardiac hypertrophy. Conclusion: Sop ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy. Hence, Sop might be an attractive candidate for the treatment of pathological cardiac hypertrophy and heart failure.

scholarly journals Knockout of AMPKα2 Blocked the Protection of Sestrin2 Overexpression Against Cardiac Hypertrophy Induced by Pressure Overload

2021 ◽  
Vol 12 ◽  
Author(s):  
Nan Zhang ◽  
Hai-Han Liao ◽  
Hong Feng ◽  
Shan-Qi Mou ◽  
Wen-Jing Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Conditional Knockout ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Genetic Toxicity ◽  
And Oxidative Stress ◽  
Dependent Pathway

Objectives: Sestrin2 (Sesn2) has been demonstrated to be a cysteine sulfinyl reductase and protects cells from multiple stress insults, including hypoxia, endoplasmic reticulum stress, and oxidative stress. However, the roles and mechanisms of Sesn2 in pressure overload-induced mouse cardiac hypertrophy have not been clearly clarified. This study intended to investigate whether sestrin2 (Sesn2) overexpression could prevent pressure overload-induced cardiac hypertrophy via an AMPKα2 dependent pathway through conditional knockout of AMPKα2.Methods and results: Sesn2 expression was significantly increased in mice hearts at 2 and 4 weeks after aortic banding (AB) surgery, but decreased to 60–70% of the baseline at 8 weeks. Sesn2 overexpression (at 3, 6, and 9 folds) showed little cardiac genetic toxicity in transgenic mice. Cardiac dysfunctions induced by pressure overload were attenuated by cardiomyocyte-specific Sesn2 overexpression when measured by echocardiography and hemodynamic analysis. Results of HE and PSR staining showed that Sesn2 overexpression significantly alleviated cardiac hypertrophy and fibrosis in mice hearts induced by pressure overload. Meanwhile, adenovirus-mediated-Sesn2 overexpression markedly suppressed angiotensin II-induced neonatal rat cardiomyocyte hypertrophy in vitro. Mechanistically, Sesn2 overexpression increased AMPKα2 phosphorylation but inhibited mTORC1 phosphorylation. The cardiac protections of Sesn2 overexpression were also via regulating oxidative stress by enhancing Nrf2/HO-1 signaling, restoring SOD activity, and suppressing NADPH activity. Particularly, we first proved the vital role of AMPKα2 in the regulation of Sesn2 with AMPKα2 knockout (AMPKα2-/-) mice and Sesn2 transgenic mice crossed with AMPKα2-/-, since Sesn2 overexpression failed to improve cardiac function, inhibit cardiac hypertrophy and fibrosis, and attenuate oxidative stress after AMPKα2 knockout.Conclusion: This study uniquely revealed that Sesn2 overexpression showed little genetic toxicity in mice hearts and inhibited mTORC1 activation and oxidative stress to protect against pressure overload-induced cardiac hypertrophy in an AMPKα2 dependent pathway. Thus, interventions through promoting Sesn2 expression might be a potential strategy for treating pathological cardiac hypertrophy and heart failure.

Abstract 72: Hydrogen Sulfide Prevents Myocardial Hypertrophy in a Klf5-dependent Manner

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Guoliang Meng ◽  
Liping Xie ◽  
Yong Ji
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Promoter Activity ◽  
Myocardial Hypertrophy ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Dependent Manner ◽  
Ang Ii ◽  
Rat Cardiomyocytes ◽  
Neonatal Rat Cardiomyocytes

Rationale: H 2 S is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel-like transcription factor (KLF) exerts diverse functions in the cardiovascular system. Objectives: The aim of present study was to investigate the effect of hydrogen sulfide (H 2 S) on myocardial hypertrophy. Methods and results: Myocardial samples of 22 patients with left ventricle hypertrophy were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats (SHR) and neonatal rat cardiomyocytes were studied for functional and signaling response to GYY4137, a H 2 S-releasing compound. Expression of cystathionine -lyase (CSE), a main enzyme for H 2 S generation in human heart, decreased in human hypertrophic myocardium, while KLF5 expression increased. In SHR treated with GYY4137 for 4 weeks, myocardial hypertrophy was inhibited as evidenced by improvement in cardiac structural parameters, heart mass index, size of cardiac myocytes and expression of atrial natriuretic peptide (ANP). Levels of oxidative stress and phosphorylation of mitogen-activated protein kinases were also decreased after H 2 S treatment. H 2 S diminished expression of the KLF5 in myocardium of SHR and in neonatal rat cardiomyocytes rendered hypertrophy by angiotensin II (Ang II). H 2 S also inhibited ANP promoter activity and ANP expression in Ang II-induced neonatal rat cardiomyocyte hypertrophy, and these effects were suppressed by KLF5 knockdown. KLF5 promoter activity was increased by Ang II stimulation, and this was reversed by H 2 S. H 2 S also decreased activity of specificity protein-1 (SP-1) binding to the KLF5 promoter and attenuated KLF5 nuclear translocation by Ang II stimulation. Conclusion: H 2 S attenuated myocardial hypertrophy, which might be related to inhibiting oxidative stress and decreasing ANP transcription activity in a KLF5-dependent manner.

Abstract 541: Dyxin/Lmcd1, A Novel LIM Protein, Is Both Necessary And Sufficient For The Induction Of Cardiomyocyte Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Derk Frank ◽  
Christiane Hanselmann ◽  
Rainer Will ◽  
Hugo A Katus ◽  
Norbert Frey
Keyword(s):  
Cardiac Hypertrophy ◽  
Molecular Mechanisms ◽  
Mrna Level ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Rat Cardiomyocytes ◽  
Hypertrophic Response ◽  
Lim Protein ◽  
A Genome ◽  
Necessary And Sufficient

Sustained cardiac hypertrophy may lead to heart failure and sudden death. While significant progress has been made in elucidating the underlying molecular mechanisms, it is believed that several molecules that modulate cardiomyocyte growth remain elusive. To identify novel candidates involved in hypertrophic signalling, we conducted a genome-wide screening experiment by subjecting neonatal rat cardiomyocytes (NRCM) to either biomechanical stretch or phenylephrine (PE) stimulation followed by microarray analyses. Among several other molecules (stretch: n=164; PE: n=238), the new LIM protein Dyxin/Lmcd1 was significantly upregulated both by stretch (5.6fold, p<0.001) and PE (2.5 fold, p<0.01). Moreover, Dyxin was markedly induced in hypertrophic hearts of transgenic mice overexpressing the phosphatase calcineurin (3.8fold on mRNA- and 2.9fold on protein level (both p<0.01)). To dissect the putative function of this novel molecule, we adenovirally overexpressed Dyxin in NRCM, which led to marked cellular hypertrophy (1.5fold increase in cell surface area, p<0.001) and induction of ANF (3.8fold, p<0.05). In addition, the calcineurin-responsive gene MCIP1.4 was found upregulated (3.2fold, p<0.001), suggesting that Dyxin activates the calcineurin pathway. In order to test whether Dyxin is also required for cardiomyocyte hypertrophy, we stimulated NRCVM with either PE or stretch and utilized adenovirus-encoded microRNAs to knock down Dyxin (−75% on protein, −85% on mRNA level). While both PE and stretch induced significant hypertrophy (+41% and +48%, p<0.001), the inhibition of Dyxin expression completely blunted the hypertrophic response to both stimuli (p<0.001). Consistently, induction of the “hypertrophic gene program” (including ANF, BNP, and alpha-skeletal actin) was abrogated. Likewise, PE-mediated upregulation of MCIP1.4 expression (7.3fold; p<0.001), was entirely prevented by the knockdown of Dyxin (0.8fold, p=n.s.). We show here that Dyxin, which has not been implicated in hypertrophy before, is significantly upregulated in cardiac hypertrophy. Moreover, it is both necessary and sufficient for cardiomyocyte hypertrophy, and this effect is mediated, at least in part by modulation of calcineurin signalling.

Abstract 1828: Dyxin/Lmcd1 Mediates Cardiac Hypertrophy Both In Vitro And In Vivo

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Derk Frank ◽  
Robert Frauen ◽  
Christiane Hanselmann ◽  
Christian Kuhn ◽  
Rainer Will ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Neonatal Rat ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
The Novel ◽  
Rat Cardiomyocytes ◽  
A Genome

In order to identify new molecular mediators of cardiomyocyte hypertrophy, we performed a genome wide mRNA microarray screen of biomechanically stretched neonatal rat cardiomyocytes (NRCM). We found the novel sarcomeric LIM protein Dyxin/Lmcd1 being significantly upregulated (5.6x, p<0.001). Moreover, Dyxin was also significantly induced in several mouse models of myocardial hypertrophy including aortic banding, calcineurin overexpression and angiotensin stimulation, suggesting a potential role as a mediator of cardiac hypertrophy. To further test this hypothesis, we adenovirally overexpressed Dyxin in NRCM which potently induced cellular hypertrophy (150%, p<0.001) and the hypertrophic gene program (ANF, BNP). Consistent with an induction of calcineurin signalling, the calcineurin-responsive gene Rcan1– 4 (MCIP1.4) was found significantly upregulated (3.2x, p<0.001). Conversely, knockdown of Dyxin (−75% on protein level) via miRNA completely blunted the hypertrophic response to hypertrophic stimuli, including stretch and PE (both p<0.001). Furthermore, PE-mediated activation of calcineurin signaling (Upregulation of Rcan1– 4 by 7.3x, p<0.001) was completely blocked by knockdown of Dyxin. To confirm these results in vivo, we next generated transgenic mice with cardiac-restricted overexpression of Dyxin using the α -MHC promoter. Despite normal cardiac function as assessed by echocardiography, adult transgenic mice displayed significant cardiac hypertrophy in morphometrical analyses (3.9 vs. 3.5 mg/g LV/heart weight, n=8–11, p<0.05). This finding was supplemented by a robust induction of the hypertrophic gene program including ANF (3.7-fold, n=6, p=0.01) and α -skeletal actin (2.8-fold, n=6, p<0.05). Likewise, Rcan1– 4 was found upregulated (+112%, n=5, p<0.05), Taken together, we show that the novel sarcomeric z-disc protein Dyxin/Lmcd1 is significantly upregulated in several models of cardiac hypertrophy and potently induces cardiomyocyte hypertrophy both in vitro and in vivo. Mechanistically, Lmcd1/Dyxin appears to signal through the calcineurin pathway.

scholarly journals Nuclear Localization Leucine-Rich-Repeat Protein 1 Deficiency Protects Against Cardiac Hypertrophy by Pressure Overload

2018 ◽  
Vol 48 (1) ◽  
pp. 75-86 ◽  
Author(s):  
Jing Zong ◽  
Fang-fang Li ◽  
Kai Liang ◽  
Rui Dai ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Nuclear Localization ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Leucine Rich Repeat ◽  
Aortic Banding ◽  
Rat Cardiomyocytes ◽  
Repeat Protein ◽  
Leucine Rich Repeat Protein

Background/Aims: Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a cytoplasmic protein, involved in autoimmune diseases, mammalian reproduction, neuronal cell death, and stroke. However, the role of NLRP1 in cardiac hypertrophy remains unclear. We used in vivo and in vitro models to investigate the effects of NLRP1 on cardiac hypertrophy. Methods: We used NLRP1-deficient mice and cultured neonatal rat cardiomyocytes with gain and loss of NLRP1 function. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements, and by pathological and molecular analysis. Results: Eight weeks after aortic banding (AB), NLRP1 deficiency significantly inhibited aortic banding–induced cardiac hypertrophy, inflammation, and fibrosis. Activation of MAPK, NF-κB, and TGF-β/Smad pathways was reduced in NLRP1-knockout (KO) mice compared with that in wild-type (WT) mice. Consistent with these results, in vitro studies, performed using cultured neonatal mouse cardiomyocytes, confirmed that NLRP1 deficiency protects against cardiomyocyte hypertrophy induced by isoproterenol (PE); this protective activity was associated with the arrest of MAPK and NF-κB signaling. Conclusions: Our data illustrates that NLRP1 plays a crucial role in the development of cardiac hypertrophy via positive regulation of the MAPK, NF-κB, and TGF-β/Smad signaling pathways.

scholarly journals Hydrogen-rich saline mitigates pressure overload-induced cardiac hypertrophy and atrial fibrillation in rats via the JAK-STAT signalling pathway

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052093641
Author(s):  
Chufeng Wang ◽  
Zezheng Pan
Keyword(s):  
Atrial Fibrillation ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Signalling Pathway ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
High Dose ◽  
Atrial Fibrosis ◽  
Rat Cardiomyocytes

Objective To investigate if hydrogen-rich saline (HRS), which has been shown to have antioxidant and anti-inflammatory properties, could mitigate cardiac remodelling and reduce the incidence of atrial fibrillation (AF) in the rat model of cardiac hypertrophy. Methods Pressure overload was induced in rats by abdominal aortic constriction (AAC). The animals were separated into four groups: sham; AAC group; AAC plus low dose HRS (LHRS); AAC plus high dose HRS (HHRS). The sham and AAC groups received normal saline intraperitoneally and the LHRS and HHRS groups received 3 or 6 ml/kg HRS daily for six weeks, respectively. In vitro research was also performed using cardiotrophin-1 (CT-1)-induced hypertrophy of cultured neonatal rat cardiomyocytes. Results Cardiac hypertrophy was successfully induced by AAC and low and high dose HRS mitigated the pressure overload as shown by lower heart and atrial weights in these treatment groups. AF incidence and duration of the HRS groups were also significantly lower in the HRS groups compared with the AAC group. Atrial fibrosis was also reduced in the HRS groups and the JAK-STAT signalling pathway was down-regulated. In vitro experiments showed that hydrogen-rich medium mitigated the CT-1-induced cardiomyocyte hypertrophy with a similar effect as the JAK specific antagonists AG490. Conclusions HRS was found to mitigate cardiac hypertrophy induced by pressure overload in rats and reduce atrial fibrosis and AF which was possibly achieved via inhibition of the JAK-STAT signalling pathway.

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