Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy

Liang, Lei; Shou, Xiling; Zhao, Haikang; Gu-qun, Ren; Wang, Jianbang; Wang, Xihui; Ai, Wenting; Maris, Jackie R.; Hueckstaedt, Lindsay K.; Ma, Aiqun; Zhang, Yingmei

doi:10.1016/j.bbadis.2014.06.027

Cited by 34 publications

(21 citation statements)

References 50 publications

(66 reference statements)

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“…HFD induced obese model has been widely used in the past, and is characterized by increased weight gain, elevated serum levels of FA and triglyceride [8, 13, 29, 31]. Here we demonstrate a tight association between myocardial FA metabolic disorder and obesity-related cardiac remodeling.…”

Section: Discussionsupporting

confidence: 53%

Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice

Zhang

Bao

Dai

et al. 2015

Cardiovasc Diabetol

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BackgroundFatty acid (FA) catabolism abnormality has been proved to play an important role in obesity-related cardiomyopathy. We hypothesized that cardiospecific suppression of CD36, the predominant membrane FA transporter, would protect against obesity-related cardiomyopathy.MethodsFour-wk-old male C57BL/6 J mice were fed with either high-fat-diet (HFD) or control-normal-diet for 2 wk. Then they were subjected to intramyocardial injection with recombinant lentiviral vectors containing short hairpin RNAs to selectively downregulate the expression of either cardiac CD36 or irrelevant gene by RNA interference. After a 10-wk continuation of the diet, biochemical, functional, morphological, histological, metabolic and molecular profiles were assessed.ResultsHFD administration elicited obesity, cardiac hypertrophy and systolic dysfunction accompanied with elevated serum levels of blood urea nitrogen (BUN), creatinine, fasting serum glucose (FSG), total cholesterol (TC) and triglyceride. Additionally, HFD consumption promoted lipid accumulation and reactive oxygen species (ROS) generation in the cardiomyocytes. Cardiospecific CD36 inhibition protected against HFD induced cardiac remodeling by decreasing heart/body weight ratio, increasing left ventricular (LV) ejection fraction and fractional shortening as well as normalizing LV diameter, without influencing body weight gain. Inhibition of cardiac CD36 also mitigated obesity induced alteration in BUN, creatinine and triglyceride, but had no effect on FSG or TC. Moreover, cardiospecific CD36 deficiency corrected myocardial lipid overaccumulation and intracellular ROS overproduction that were induced by HFD feeding.ConclusionsCardiospecific CD36 inhibition protects against the aggravation of cardiac functional and morphological changes associated with HFD induced obesity. CD36 represents a potential therapeutic target for obesity cardiomyopathy.

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Section: Discussionsupporting

confidence: 53%

Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice

Zhang

Bao

Dai

et al. 2015

Cardiovasc Diabetol

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“…Fractional shortening was calculated from LV end-diastolic (LVEDD) and end-systolic (LVESD) diameters using the equation (LVEDD-LVESD)/LVEDD*100. Heart rates were averaged over ten consecutive cycles [30].…”

Section: Echocardiographic Assessmentmentioning

confidence: 99%

“…Only rod-shaped cardiomyocytes with clear edges were selected for mechanical and intracellular Ca 2? studies [30].…”

Section: Cardiomyocytes Isolationmentioning

confidence: 99%

“…IonOptix SoftEdge software was used to capture changes in cell length during shortening and relengthening. Cell shortening and relengthening were assessed using the following indices: peak shortening (PS)-the amplitude myocytes shortened on electrical stimulation, which is indicative of peak ventricular contractility; time-to-peak shortening (TPS)-the duration of myocyte shortening, which is indicative of contraction duration; time-to-90 % relengthening (TR 90 )-the duration to reach 90 % relengthening, which represents cardiomyocyte relaxation duration (90 % rather 100 % relengthening was used to avoid noisy signal at baseline concentration); and maximal velocities of shortening (?dL/dt) and relengthening (-dL/dt)-maximal slope (derivative) of shortening and relengthening phases, which are indicatives of maximal velocities of ventricular pressure rise/fall [30].…”

Section: Cell Shortening/relengtheningmentioning

confidence: 99%

“…Fluorescence decay time (both single and bi-exponential decay rates) was measured as an indication of intracellular Ca 2? clearing rate [30].…”

Section: Intracellular Ca 21 Transientsmentioning

confidence: 99%

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Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction

Wang

Zheng

et al. 2015

Cardiovasc Toxicol

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Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ETA) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ETA receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteinsfor biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, overt apoptosis and mitochondrial damage. ETA receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ETA receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ETA receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage.

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Autophagy in cardiac metabolic control: Novel mechanisms for cardiovascular disorders

Yang

Zhao

Yang

et al. 2016

Cell Biology International

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As an extensively studied quality control system, autophagy is responsible for clearance of dysfunctional organelles and damaged marcomolecules in cells. In addition to its biological recycling function, autophagy plays a significant role in the pathogenesis of metabolic syndromes such as obesity and diabetes. In particular, metabolic disorders contribute to cardiovascular disease development. As energy required to maintain cardiac cells functional is immense, disturbances in the balance between anabolic and catabolic metabolism possibly contribute to cardiovascular disorders. Therefore, an urgent need to expand our knowledge on the role of autophagy on the metabolic regulation of hearts emerges. In this review, the potential relationship between autophagic activity and cardiac metabolism is explored and we also discuss how dysregulated autophagy leads to severe cardiac disorders from the perspective of metabolic control.

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Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy

Cited by 34 publications

References 50 publications

Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice

Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice

Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction

Autophagy in cardiac metabolic control: Novel mechanisms for cardiovascular disorders

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