Relationship between oxidative stress and nuclear factor‑erythroid‑2‑related factor 2 signaling in diabetic cardiomyopathy (Review)

Wu, Xia; Huang, Leitao; Liu, Jichun

doi:10.3892/etm.2021.10110

Cited by 25 publications

(23 citation statements)

References 141 publications

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“…Nrf-2 is a pivotal transcriptional factor that regulates the cardiac homeostasis via suppressing oxidative stress. Emerging evidence has confirmed its important function in regulating ischemic heart disease, heart failure, myocardial infarction, atrial fibrillation, and myocarditis [ 42 ]. HO-1 has been extensively recognized as the downstream of Nrf-2 and plays a key role in cell adaptation to stressors through the antioxidant, antiapoptotic, and anti-inflammatory properties of its metabolic products [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

et al. 2021

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Rationale. Pathological cardiac remodeling serves as a vital mechanism during the progression from myocardial infarction (MI) to chronic heart failure (CHF). Nobiletin (NOB), an active monomer extracted from the peel of citrus fruit, has been reported to have beneficial effects in cardiovascular diseases. Our study was aimed at describing the specific mechanisms through which NOB protects against pathological cardiac remodeling after MI. Materials and Methods. C57BL/6 mice were treated with coronary artery ligation to generate an MI model, followed by treatment for 3 weeks with NOB (50 mg/kg/d) or vehicle (50 mg/kg/d), with or without the peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor T0070907 (1 mg/kg/d). Cardiac function (echocardiography, survival rate, Evans blue, and triphenyl tetrazolium chloride staining), fibrosis (Masson’s trichrome staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB)), hypertrophy (haematoxylin-eosin staining, wheat germ agglutinin staining, and qRT-PCR), and apoptosis (WB and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining) were evaluated. Hypoxia-induced apoptosis (TUNEL, WB) and phenylephrine- (PE-) induced pathological hypertrophy (immunofluorescence staining, qRT-PCR) models were established in primary neonatal rat ventricular myocytes (NRVMs). The effects of NOB with or without T0070907 were examined for the expression of PPARγ and PPARγ coactivator 1α (PGC1α) by WB in mice and NRVMs. The potential downstream effectors of PPARγ were further analyzed by WB in mice. Results. Following MI in mice, NOB intervention enhanced cardiac function across three predominant dimensions of pathological cardiac remodeling, which reflected in decreasing cardiac fibrosis, apoptosis, and hypertrophy decompensation. NOB intervention also alleviated apoptosis and hypertrophy in NRVMs. NOB intervention upregulated PPARγ and PGC1α in vivo and in vitro. Furthermore, the PPARγ inhibitor abolished the protective effects of NOB against pathological cardiac remodeling during the progression from MI to CHF. The potential downstream effectors of PPARγ were nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1). Conclusions. Our findings suggested that NOB alleviates pathological cardiac remodeling after MI via PPARγ and PGC1α upregulation.

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Section: Discussionmentioning

confidence: 99%

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

et al. 2021

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“…The Nrf2 signaling pathway is closely linked to the development of cardiac diseases such as AF, diabetic cardiomyopathy, myocarditis, heart failure, and ischemic heart disease [109]. Recent data indicate that the cellular redox state is subject to regulation by miRNAs through modulating Nrf2-dependent anti-oxidant gene expression or attenuating activities of ROS handling enzymes [110].…”

Section: Redox-regulated Signaling Pathwaysmentioning

confidence: 99%

Atrial Cardiomyopathy: Pathophysiology and Clinical Consequences

Goette

Lendeckel

2021

Cells

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Around the world there are 33.5 million patients suffering from atrial fibrillation (AF) with an annual increase of 5 million cases. Most AF patients have an established form of an atrial cardiomyopathy. The concept of atrial cardiomyopathy was introduced in 2016. Thus, therapy of underlying diseases and atrial tissue changes appear as a cornerstone of AF therapy. Furthermore, therapy or prevention of atrial endocardial changes has the potential to reduce atrial thrombogenesis and thereby cerebral stroke. The present manuscript will summarize the underlying pathophysiology and remodeling processes observed in the development of an atrial cardiomyopathy, thrombogenesis, and atrial fibrillation. In particular, the impact of oxidative stress, inflammation, diabetes, and obesity will be addressed.

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“…The long-term exposure to hyperglycemia in the heart could produce the amount of oxidative stress induce in the overproduction of ROS, which is derived from NOX, especially NOX2 and NOX4 which are important sources of O 2− and H 2 O 2 ; all of these responses result into a serious deteriorating consequence, such as mitochondrial dysfunction, advanced glycation end products, calcium overload, lipotoxicity, and inflammation, all eventually promote the progression of DCM, and moreover, the oxidative stress is also toxic for systolic and endothelial dysfunction and cardiac cell death and necrosis; thereby the reduction of oxidative stress is an attractive target for cure of cardiac diseases. PI3K/AKT signaling pathway has been reported to suppress inflammation and mediate oxidative stress, thereby any interfering factor with antiinflammatory or antioxidant features may be beneficial for DCM [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of miR-372-3p Inhibits the Development of Diabetic Cardiomyopathy by Accelerating Angiogenesis via Activating the PI3K/AKT/mTOR/HIF-1α Signaling Pathway and Suppressing Oxidative Stress

Han

Zhao

Han

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. DCM is the most common and malignant complication of diabetes. It is characterized by myocardial dilatation, hypertrophy, fibrosis, ventricular remodeling, and contractile dysfunction. Although many studies have demonstrated the function of miRNAs in the progression of DCM, but the specific role of miR-372-3p in DCM remains unknown. Methods. C57/BL6J mice were used to construct mouse models of DCM by intraperitoneal injection of STZ (50 mg/kg/d) for 5 consecutive days. Then the mice were randomly divided into model group (intramyocardial injection of empty lentivirus) and miR-372-3p KD group (intramyocardial injection of miR-372-3p KD lentivirus at 10 9 /mouse). Besides, the control group (injection of 0.9% normal saline) was also set up. LY294002, a PI3K inhibitor, was employed in the current study. Western blotting, immunofluorescence staining, quantitative ultrasound method, Masson's trichrome staining, and bioinformatics analysis were performed. Results. It was found that miR-372-3p KD significantly improved left ventricular dysfunction and cardiac hypertrophy in DCM mice. Furthermore, it also improved myocardial interstitial fibrosis and remodeling in DCM mice. Immunofluorescence staining and RT-qPCR revealed that miR-372-3p KD might accelerate cardiac remodeling by increasing angiogenesis in DCM mice. Western blotting results revealed that miR-372-3p was an upstream target of the PI3K/ AKT-mTOR and HIF-1α signals, as well as NOX2, NOX4, which were responsible for angiogenesis in DCM mice. Besides, the in vitro experiment showed that LY294002 markedly diminished the increased expression levels of p-PI3K, AKT, p-mTOR, p-P70S6K, HIF-1α, NOX2, and NOX4 in the model group and the miR-372-3p KD group, suggesting that PI3K signaling pathway and oxidative stress are involved in miR-372-3p KD-induced angiogenesis in HG-stimulated C166 cells. Conclusions. MiR-372-3p KD inhibits the development of DCM via activating the PI3K/AKT/mTOR/HIF-1α signaling pathway or suppressing oxidative stress. This offers an applicable biomarker for DCM treatment.

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Relationship between oxidative stress and nuclear factor‑erythroid‑2‑related factor 2 signaling in diabetic cardiomyopathy (Review)

Cited by 25 publications

References 141 publications

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

Atrial Cardiomyopathy: Pathophysiology and Clinical Consequences

Knockdown of miR-372-3p Inhibits the Development of Diabetic Cardiomyopathy by Accelerating Angiogenesis via Activating the PI3K/AKT/mTOR/HIF-1α Signaling Pathway and Suppressing Oxidative Stress

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