scholarly journals Myricetin Possesses Potential Protective Effects on Diabetic Cardiomyopathy through Inhibiting IκBα/NFκB and Enhancing Nrf2/HO-1

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Hai-han Liao ◽  
Jin-xiu Zhu ◽  
Hong Feng ◽  
Jian Ni ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Interstitial Fibrosis ◽  
Cardiac Injury ◽  
Specific Treatment ◽  
Neonatal Rat ◽  
Protective Effects ◽  
Rat Cardiomyocytes ◽  
Positive Nucleus

Diabetic cardiomyopathy (DCM) is associated with a greater risk of mortality in patients with diabetes mellitus. Currently, no specific treatment has been suggested for DCM treatment. This study demonstrated that myricetin (M) attenuated DCM-associated cardiac injury in mice subjected to streptozotocin (SZT) and in neonatal rat cardiomyocytes (NRCM) challenged with high glucose.In vivoinvestigation demonstrated 6 months of M treatment (200 mg/kg/d) significantly alleviated cardiac hypertrophy, apoptosis, and interstitial fibrosis. Mechanically, M treatment significantly increased the activity of Nrf2/HO-1 pathway, strengthening antioxidative stress capacity evidenced by reversed activities of GPx and SOD, and decreased MDA production. M treatment also inhibited IκBα/NF-κB pathway, resulting in reduced secretion of inflammation cytokines including IL-1β, TNF-α, and IL-6. Besides, the TGFβ/Smad3 signaling was also blunted in DCM mice treated with M. These beneficial effects of M treatment protected cardiomyocytes from apoptosis as shown by decreased TUNEL-positive nucleus, c-caspase 3, and Bax. Similar effects of M treatment could be reproduced in NRCM treated with high glucose. Furthermore, through silencing Nrf2 in NRCM, we found that the regulation of IκBα/NFκB by M was independent on its function on Nrf2. Thus, we concluded that M possesses potential protective effects on DCM through inhibiting IκBα/NFκB and enhancing Nrf2/HO-1.

scholarly journals Osteocrin, a novel myokine, prevents diabetic cardiomyopathy via restoring proteasomal activity

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xin Zhang ◽  
Can Hu ◽  
Xiao-Pin Yuan ◽  
Yu-Pei Yuan ◽  
Peng Song ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Injury ◽  
Neonatal Rat ◽  
Protective Effects ◽  
Rat Cardiomyocytes ◽  
Proteasomal Activity ◽  
Virus Serotype

AbstractProteasomal activity is compromised in diabetic hearts that contributes to proteotoxic stresses and cardiac dysfunction. Osteocrin (OSTN) acts as a novel exercise-responsive myokine and is implicated in various cardiac diseases. Herein, we aim to investigate the role and underlying molecular basis of OSTN in diabetic cardiomyopathy (DCM). Mice received a single intravenous injection of the cardiotrophic adeno-associated virus serotype 9 to overexpress OSTN in the heart and then were exposed to intraperitoneal injections of streptozotocin (STZ, 50 mg/kg) for consecutive 5 days to generate diabetic models. Neonatal rat cardiomyocytes were isolated and stimulated with high glucose to verify the role of OSTN in vitro. OSTN expression was reduced by protein kinase B/forkhead box O1 dephosphorylation in diabetic hearts, while its overexpression significantly attenuated cardiac injury and dysfunction in mice with STZ treatment. Besides, OSTN incubation prevented, whereas OSTN silence aggravated cardiomyocyte apoptosis and injury upon hyperglycemic stimulation in vitro. Mechanistically, OSTN treatment restored protein kinase G (PKG)-dependent proteasomal function, and PKG or proteasome inhibition abrogated the protective effects of OSTN in vivo and in vitro. Furthermore, OSTN replenishment was sufficient to prevent the progression of pre-established DCM and had synergistic cardioprotection with sildenafil. OSTN protects against DCM via restoring PKG-dependent proteasomal activity and it is a promising therapeutic target to treat DCM.

scholarly journals Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Kaifeng Li ◽  
Mengen Zhai ◽  
Liqing Jiang ◽  
Fan Song ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Protective Effects ◽  
Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

scholarly journals The 5-Lipoxygenase Inhibitor Zileuton Protects Pressure Overload-Induced Cardiac Remodeling via Activating PPARα

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Qing-Qing Wu ◽  
Wei Deng ◽  
Yang Xiao ◽  
Jiao-Jiao Chen ◽  
Chen Liu ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Pressure Overload ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Dependent Manner ◽  
Protective Effects ◽  
Lipoxygenase Inhibitor ◽  
Rat Cardiomyocytes ◽  
Nrf2 Activation

Zileuton has been demonstrated to be an anti-inflammatory agent due to its well-known ability to inhibit 5-lipoxygenase (5-LOX). However, the effects of zileuton on cardiac remodeling are unclear. In this study, the effects of zileuton on pressure overload-induced cardiac remodeling were investigated and the possible mechanisms were examined. Aortic banding was performed on mice to induce a cardiac remodeling model, and the mice were then treated with zileuton 1 week after surgery. We also stimulated neonatal rat cardiomyocytes with phenylephrine (PE) and then treated them with zileuton. Our data indicated that zileuton protected mice from pressure overload-induced cardiac hypertrophy, fibrosis, and oxidative stress. Zileuton also attenuated PE-induced cardiomyocyte hypertrophy in a time- and dose-dependent manner. Mechanistically, we found that zileuton activated PPARα, but not PPARγ or PPARθ, thus inducing Keap and NRF2 activation. This was confirmed with the PPARα inhibitor GW7647 and NRF2 siRNA, which abolished the protective effects of zileuton on cardiomyocytes. Moreover, PPARα knockdown abolished the anticardiac remodeling effects of zileuton in vivo. Taken together, our data indicate that zileuton protects against pressure overload-induced cardiac remodeling by activating PPARα/NRF2 signaling.

scholarly journals Traditional Chinese Medication Qiliqiangxin Attenuates Diabetic Cardiomyopathy via Activating PPARγ

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaodong Wu ◽  
Ting Zhang ◽  
Ping Lyu ◽  
Mengli Chen ◽  
Gehui Ni ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Neonatal Rat ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Protective Mechanisms ◽  
Rat Cardiomyocytes ◽  
Induced Apoptosis ◽  
Hematoxylin Eosin

Background: Diabetic cardiomyopathy is the primary complication associated with diabetes mellitus and also is a major cause of death and disability. Limited pharmacological therapies are available for diabetic cardiomyopathy. Qiliqiangxin (QLQX), a Chinese medication, has been proven to be beneficial for heart failure patients. However, the role and the underlying protective mechanisms of QLQX in diabetic cardiomyopathy remain largely unexplored.Methods: Primary neonatal rat cardiomyocytes (NRCMs) were treated with glucose (HG, 40 mM) to establish the hyperglycemia-induced apoptosis model in vitro. Streptozotocin (STZ, 50 mg/kg/day for 5 consecutive days) was intraperitoneally injected into mice to establish the diabetic cardiomyopathy model in vivo. Various analyses including qRT-PCR, western blot, immunofluorescence [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining] histology (hematoxylin–eosin and Masson's trichrome staining), and cardiac function (echocardiography) were performed in these mice. QLQX (0.5 μg/ml in vitro and 0.5 g/kg/day in vivo) was used in this study.Results: QLQX attenuated hyperglycemia-induced cardiomyocyte apoptosis via activating peroxisome proliferation-activated receptor γ (PPARγ). In vivo, QLQX treatment protected mice against STZ-induced cardiac dysfunction and pathological remodeling.Conclusions: QLQX attenuates diabetic cardiomyopathy via activating PPARγ.

scholarly journals Protective Effects of Low-Frequency Magnetic Fields on Cardiomyocytes from Ischemia Reperfusion InjuryviaROS and NO/ONOO−

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sai Ma ◽  
Zhengxun Zhang ◽  
Fu Yi ◽  
Yabin Wang ◽  
Xiaotian Zhang ◽  
...  
Keyword(s):  
Magnetic Fields ◽  
Cell Viability ◽  
Ischemia Reperfusion ◽  
Low Frequency ◽  
Neonatal Rat ◽  
Ros Generation ◽  
No Production ◽  
Protective Effects ◽  
Rat Cardiomyocytes

Background. Cardiac ischemia reperfusion (I/R) injury is associated with overproduction of reactive oxygen species (ROS). Low frequency pulse magnetic fields (LFMFs) have been reported to decrease ROS generation in endothelial cells. Whether LFMFs could assert protective effects on myocardial from I/R injuryviaROS regulation remains unclear.Methods. To simulatein vivocardiac I/R injury, neonatal rat cardiomyocytes were subjected to hypoxia reoxygenation (H/R) with or without exposure to LFMFs. Cell viability, apoptosis index, ROS generation (includingO2-and ONOO−), and NO production were measured in control, H/R, and H/R + LFMF groups, respectively.Results. H/R injury resulted in cardiomyocytes apoptosis and decreased cell viability, whereas exposure to LFMFs before or after H/R injury significantly inhibited apoptosis and improved cell viability (P<0.05). LFMFs treatment could suppress ROS (includingO2-and ONOO−) generation induced by H/R injury, combined with decreased NADPH oxidase activity. In addition, LFMFs elevated NO production and enhanced NO/ONOO−balance in cardiomyocytes, and this protective effect wasviathe phosphorylation of endothelial nitric oxide synthase (eNOS).Conclusion. LFMFs could protect myocardium against I/R injuryviaregulating ROS generation and NO/ONOO−balance. LFMFs treatment might serve as a promising strategy for cardiac I/R injury.

scholarly journals Bailcalin Protects against Diabetic Cardiomyopathy through Keap1/Nrf2/AMPK-Mediated Antioxidative and Lipid-Lowering Effects

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Ran Li ◽  
Yuan Liu ◽  
Ying-guang Shan ◽  
Lu Gao ◽  
Fang Wang ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Neonatal Rat ◽  
Lipid Lowering ◽  
Cardiomyocyte Hypertrophy ◽  
Rat Cardiomyocytes ◽  
Cardiac Functions ◽  
Enhanced Expression ◽  
Induced Apoptosis

Previous studies demonstrated that Bailcalin (BAI) prevented cardiac injuries under different disease models. Whether BAI protected against type 2 diabetes mellitus- (T2DM-) associated cardiomyopathy was investigated in this study. T2DM was established by the combination of streptozotocin injection and high-fat diet in mice. BAI was administered daily for 6 months. After evaluating cardiac functions, mice hearts were removed and processed for morphological, biochemical, and molecular mechanism analyses. Neonatal rat cardiomyocytes (NRCM) were isolated and treated with high glucose and palmitate (HG/Pal) for in vitro investigation. BAI significantly ameliorated T2DM-induced cardiomyocyte hypertrophy, interstitial fibrosis, and lipid accumulation accompanied by markedly improved cardiac functions in diabetic mice. Mechanically, BAI restored decreased phosphorylation of AMPK and enhanced expression and nuclei translocation of Nrf2. In in vitro experiments, BAI also prevented NRCM from HG/Pal-induced apoptosis and oxidative stress injuries by increasing p-AMPK and Nrf2 accumulation. The means by which BAI restored p-AMPK seemed to be related to the antioxidative effects of Nrf2 after silencing AMPK or Nrf2 in NRCM. Furthermore, BAI regulated Nrf2 by inhibiting Nrf2 ubiquitination and consequent degradation mediated by Keap1. This study showed that BAI alleviated diabetes-associated cardiac dysfunction and cardiomyocyte injuries in vivo and in vitro via Keap1/Nrf2/AMPK-mediated antioxidation and lipid-lowering effects. BAI might be a potential adjuvant drug for diabetes cardiomyopathy treatment.

scholarly journals FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dezhong Wang ◽  
Yuan Yin ◽  
Shuyi Wang ◽  
Tianyang Zhao ◽  
Fanghua Gong ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Metabolic Regulation ◽  
Cardiac Injury ◽  
Serum Levels ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cardiac Tissues ◽  
Beneficial Effects

AbstractAs a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

Abstract 214: MicroRNA-451 Aggravates Lipotoxic Cardiomyopathy Through Suppression of the LKB1/AMPK Signaling Pathway

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Yasuhide Kuwabara ◽  
Takahiro Horie ◽  
Osamu Baba ◽  
Toru Kita ◽  
Takeshi Kimura ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Diabetic Cardiomyopathy ◽  
Calcium Binding ◽  
Saturated Fatty Acids ◽  
Mammalian Target Of Rapamycin ◽  
Neonatal Rat ◽  
Albumin Concentration ◽  
Dependent Manner ◽  
Ceramide Level

Rationale: In some type 2 diabetes mellitus (T2D) patients without hypertension, cardiac hypertrophy and attenuated cardiac function are observed, and this insult is termed “diabetic cardiomyopathy.” Tons of evidence suggests that microRNAs are involved in cardiac diseases. However, the functions of microRNAs in the diabetic cardiomyopathy induced by T2D and obesity are not fully understood. Methods and Results: C57BL/6 mice were fed a high-fat diet (HFD) for 20 weeks, which induced obesity and T2D. MicroRNA microarray and real-time PCR revealed that miR-451 levels were significantly increased in the T2D mouse hearts (n=4-5, p<0.05). Because excess supply of saturated fatty acids is a cause of diabetic cardiomyopathy, we stimulated neonatal rat cardiac myocytes (NRCMs) with palmitate in physiological albumin concentration and confirmed that miR-451 expression was increased in a dose-dependent manner (n=6-12, p<0.01). Loss of miR-451 function ameliorated palmitate-induced lipotoxicity in NRCMs (n=4, p<0.05). Calcium-binding protein 39 (Cab39) is a scaffold protein of liver kinase B1 (LKB1), an upstream kinase of AMP-activated protein kinase (AMPK). Cab39 was a direct target of miR-451 in NRCMs and Cab39 overexpression rescued the palmitate-induced lipotoxicity in NRCMs (n=4, p<0.01). To clarify miR-451 functions in vivo, we generated cardiomyocyte-specific miR-451 knockout (cKO) mice. HFD-induced cardiac hypertrophy and contractile reserves were ameliorated in cKO mice compared with HFD-fed control mice. Protein levels of Cab39 and phosphorylated AMPK were increased and phosphorylated mammalian target of rapamycin (mTOR) was reduced in HFD-fed cKO mouse hearts compared with HFD-fed control mouse hearts (n=10-12, p<0.05). We also measured the lipotoxic intermediates, triglyceride and ceramide, in these mouse hearts using HPLC-evaporative light scattering detector (ELSD). Although there was no difference in triglyceride levels (n=3-5), ceramide level was decreased in HFD-fed cKO mice compared with HFD-fed control mice (n=3-5, p<0.05). Conclusions: Our results indicate that miR-451 exacerbates diabetic cardiomyopathy. miR-451 is a potential therapeutic target for cardiac disease caused by T2D and obesity.

Abstract 1582: Adenosine A3 Receptor Deficiency Exerts Unanticipated Protective Effects on Pressure Overloaded-Induced Left Ventricular Hypertrophy and Dysfunction in Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Zhongbing Lu ◽  
John Fassett ◽  
Xin Xu ◽  
Xinli Hu ◽  
Guangshuo Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Heart Association ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Protective Effects ◽  
Rat Cardiomyocytes ◽  
Extracellular Adenosine ◽  
Myocardial Oxidative Stress

Endogenous adenosine can protect the overloaded heart against the development of hypertrophy and heart failure, but the contribution of A 1 receptors (A 1 R) and A 3 receptors(A 3 R) is not known. To test the hypothesis A 1 R and A 3 R can protect the heart against systolic overload, we exposed A 3 R gene deficient (A 3 R KO) mice and A 1 R KO mice to transverse aortic constriction (TAC). Contrary to our hypothesis, A 3 R KO attenuated 5 weeks TAC-induced left ventricular (LV) hypertrophy (ratio of ventricular mass/body weight increased to 7.6 ±0.3 mg/g in wild type (Wt) mice as compared with 6.3±0.4 mg/g in KO), fibrosis and dysfunction (LV ejection fraction decreased to 43±2.5% and 55±4.2% in Wt and KO mice, respectively). A 3 R KO also attenuated the TAC-induced increases of myocardial ANP and the oxidative stress markers 3-nitrotyrosine(3-NT ) and 4-hydroxynonenal. In addition, A 3 R KO significantly attenuated TAC-induced activation of multiple MAP kinase pathways, and the activation of Akt-GSK signaling pathway. In contrast, A 1 R-KO increased TAC-induced mortality, but did not alter ventricular hypertrophy or dysfunction compared to Wt mice. In mice in which extracellular adenosine production was impaired by CD73 KO, TAC caused greater hypertrophy and dysfunction, and increased myocardial 3-NT, indicates that extracellular adenosine protects heart against TAC-induced ventricular oxidative stress and hypertrophy. In neonatal rat cardiomyocytes induced to hypertrophy with phenylephrine, the adenosine analogue 2-chloroadenosine (CADO) reduced cell area, protein synthesis, ANP and 3-NT. Antagonism of A3R significantly potentiated the anti-hypertrophic effects of CADO. Our data demonstrated that extracellular adenosine exerts protective effects on the overloaded heart, but A 3 R act counter to the protective effect of adenosine. The data suggest that selective attenuation of A 3 R activity might be a novel approach to attenuate pressure overload-induced myocardial oxidative stress, LV hypertrophy and dysfunction. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).

Abstract 15445: The Sirtuin SIRT3 Blocks Doxorubicin-induced Cardiac Hypertrophic Response of Mice

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Vinodkumar Pillai ◽  
Sadhana Samant ◽  
Nagalingam Sundaresan ◽  
Gene Kim ◽  
Mahesh P Gupta
Keyword(s):  
Negative Regulator ◽  
Neonatal Rat ◽  
Whole Body ◽  
Wild Type ◽  
Electron Microscopic ◽  
Specific Expression ◽  
Rat Cardiomyocytes ◽  
Fluorescent Intensity ◽  
Hypertrophic Response

Background and objective: Doxorubicin is a chemotherapeutic drug widely used to treat variety of cancers. One of the serious side effects of doxorubicin is its toxicity to the heart. Previously, we have shown that overexpression of SIRT3 blocks the hypertrophic response of the heart to agonist treatments. This study was undertaken to investigate whether SIRT3 can also attenuate the doxorubicin-induced cardiac hypertrophic response in mice. Methods and results: Neonatal rat cardiomyocytes overexpressed with SIRT3 and treated with doxorubicin (10μM) showed 28% reduced mean fluorescent intensity for CM-H 2 DCFDA dye, compared to mock infected control cells treated with doxorubicin, thus suggesting that SIRT3 was capable of blocking doxorubicin-induced ROS synthesis in cardiomyocytes. To examine the cardioprotective effects of SIRT3 in doxorubicin-induced cardiotoxicity in vivo ; we used a cumulative dose of 15mg/kg of doxorubicin for two different time points. One group of mice was treated intraperitoneally with 5mg/kg doxorubicin or an equal volume of saline every two weeks for a total of three doses. Transgenic mice having cardiac specific expression of SIRT3 (SIRT3-Tg) showed 33% reduced HW/BW ratio compared to control mice. Echocardiographic evaluation of hearts showed significantly reduced fractional shortening in control mice, compared to SIRT3-Tg mice (24.6 vs 34.7 %, P<0.05). SIRT3-Tg mice also showed significantly reduced fetal gene expression for ANF, βMHC and collagen-1 as determined by RT-PCR. Masson’s trichrome staining showed significantly reduced fibrosis in doxorubicin treated SIRT3-Tg mice compared to its control. Furthermore, electron microscopic analysis showed preserved mitochondrial and sarcomeres structures in doxorubicin treated SIRT3-Tg hearts, whereas in wild-type hearts these structures were highly disorganized. Second group of mice that received 15mg/kg dose for two weeks also showed similar results. Contrary to this, whole body SIRT3 knockout mice showed exacerbated cardiac hypertrophic response compared to wild-type mice in response to doxorubicin treatment. Conclusion: These results demonstrated that SIRT3 is an endogenous negative regulator of doxorubicin-induced cardiac hypertrophic response.

Sign in / Sign up

Export Citation Format

Share Document