Oxidative Stress and Cardiac Remodeling: An Updated Edge

Rababa’h, Abeer; Guillory, Ashley N.; Mustafa, Rima; Hijjawi, Tamara

doi:10.2174/1573403x14666180111145207

Cited by 97 publications

(73 citation statements)

References 50 publications

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“…In addition to inflammation, obesity results in oxidative stress produced by excessive lipid peroxidation in mitochondria due to elevated glucose and lipid levels 30 . The accumulation of oxidative damage may contribute to cardiac inflammation and remodeling 31 but the induction of antioxidants HO-1 and NQO1 exert anti-oxidative and anti-inflammatory functions 32 . HO-1 confers protection against cardiac injury, and its catalytic by-products (biliverdin and carbon monoxide) have anti-hypertrophic effects 33 .…”

Section: Discussionmentioning

confidence: 99%

Caloric restriction reverses left ventricular hypertrophy through the regulation of cardiac iron homeostasis in impaired leptin signaling mice

Lee

Choi

et al. 2020

Sci Rep

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Leptin-deficient and leptin-resistant mice manifest obesity, insulin resistance, and left ventricular hypertrophy (LVH); however, LVH's mechanisms are not fully understood. Cardiac iron dysregulation has been recently implicated in cardiomyopathy. Here we investigated the protective effects of caloric restriction on cardiac remodeling in impaired leptin signaling obese mice. RNA-seq analysis was performed to assess the differential gene expressions in the heart of wild-type and ob/ob mice. In particular, to investigate the roles of caloric restriction on iron homeostasis-related gene expressions, 10-week-old ob/ob and db/db mice were assigned to ad libitum or calorie-restricted diets for 12 weeks. Male ob/ob mice exhibited LVH, cardiac inflammation, and oxidative stress. Using RNA-seq analysis, we identified that an iron uptake-associated gene, transferrin receptor, was upregulated in obese ob/ob mice with LVH. Caloric restriction attenuated myocyte hypertrophy, cardiac inflammation, fibrosis, and oxidative stress in ob/ob and db/db mice. Furthermore, we found that caloric restriction reversed iron homeostasis-related lipocalin 2, divalent metal transporter 1, transferrin receptor, ferritin, ferroportin, and hepcidin expressions in the heart of ob/ob and db/db mice. These findings demonstrate that the cardioprotective effects of caloric restriction result from the cellular regulation of iron homeostasis, thereby decreasing oxidative stress, inflammation, and cardiac remodeling. We suggest that decreasing iron-mediated oxidative stress and inflammation offers new therapeutic approaches for obesityinduced cardiomyopathy.Disruption of leptin signaling leads to obesity-induced cardiac remodeling 1,2 , and this progression of cardiac hypertrophy to heart failure is a major contributor to morbidity and mortality in obese patients 3 . Although the pathophysiology of cardiac remodeling in obesity is complex, leptin-deficient (ob/ob) and leptin-resistant (db/ db) signaling serve an important role in obesity-associated left ventricular hypertrophy (LVH) 1,2,4 . The cardiomyopathy that stems from disruption of leptin signaling is due to several factors including insulin resistance, myocardial steatosis, inflammation, oxidative stress, and direct effects of deficiencies in leptin or leptin receptors 1,5,6 . However, the precise role of leptin on obesity-induced cardiomyopathy is not completely understood.Effect of CR on cardiac iron uptake in ob/ob and db/db mice. Due to our observation of elevated cardiac ferrous iron levels in ob/ob mice (Fig. 2f), we examined regulation of iron uptake-related genes via qRT-PCR. LCN2, DMT1, Tfrc, and L-ferritin mRNA levels were significantly lower in ob/ob+CR mice relative to ob/ob and db/db mice fed ad libitum (Figs. S6 and S8). Although the level of 24p3R mRNA in the hearts of ob/ob mice was significantly reduced by CR, we did not observe the same pattern in db/db mice (Figs. S6b and S8b). In addition, CR did not cause the change of iron uptake-related genes in WT and db/m mice ( Figs. S...

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Section: Discussionmentioning

confidence: 99%

Caloric restriction reverses left ventricular hypertrophy through the regulation of cardiac iron homeostasis in impaired leptin signaling mice

Lee

Choi

et al. 2020

Sci Rep

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“…For example, dysfunctions of the various complexes of the mitochondrial respiratory chain are also observed in the non-infarcted zone of the myocardium in in vivo models of myocardial infarction, associated with a decrease in mitochondrial respiration [55]. These disruptions to the mitochondrial respiratory chain are associated with increased oxidative stress and ROS production, leading to the activation of many protein kinases and transcription factors involved in hypertrophic signaling [56] (Figure 4).…”

Section: Mitochondrial Oxidative Stressmentioning

confidence: 99%

Oxidative Stress in Cardiovascular Diseases

et al. 2020

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Reactive oxygen species (ROS) are subcellular messengers in signal transductions pathways with both beneficial and deleterious roles. ROS are generated as a by-product of mitochondrial respiration or metabolism or by specific enzymes such as superoxide dismutases, glutathione peroxidase, catalase, peroxiredoxins, and myeloperoxidases. Under physiological conditions, the low levels of ROS production are equivalent to their detoxification, playing a major role in cellular signaling and function. In pathological situations, particularly atherosclerosis or hypertension, the release of ROS exceeds endogenous antioxidant capacity, leading to cell death. At cardiovascular levels, oxidative stress is highly implicated in myocardial infarction, ischemia/reperfusion, or heart failure. Here, we will first detail the physiological role of low ROS production in the heart and the vessels. Indeed, ROS are able to regulate multiple cardiovascular functions, such as cell proliferation, migration, and death. Second, we will investigate the implication of oxidative stress in cardiovascular diseases. Then, we will focus on ROS produced by NAPDH oxidase or during endothelial or mitochondrial dysfunction. Given the importance of oxidative stress at the cardiovascular level, antioxidant therapies could be a real benefit. In the last part of this review, we will detail the new therapeutic strategies potentially involved in cardiovascular protection and currently under study.

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“…Oxidative stress is closely related to cardiac hypertrophy and oxidative stress is considered to be a major inducer for the signal transduction in cardiac cells pathological conditions [28]. Thus, a large number of studies have shown that inhibition of oxidative stress can significantly prevent and improve cardiac hypertrophy [29][30][31].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-129-5p targets keap-1 to protect against cardiomyocyte hypertrophy via Nrf2 pathway

Zhang

et al. 2020

Preprint

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Background: Cardiac hypertrophy is a common pathological process of many cardiac diseases and persistent cardiac hypertrophy is the main cause of heart failure and sudden cardiogenic death. It is of great value to elucidate the mechanism of cardiac hypertrophy for better prevention and treatment. Methods: The protein levels were measured by western blotting or RT-qPCR. cardiomyocytes hypertrophy was evaluated by [3H]-leucine incorporation assay. oxidative stress was measured by corresponding detection kits. The target relationship was measured by Luciferase reporter gene assay. Morphological change of cardiomyocyte was measured by immunofluorescence staining. Results: In our study, we for the first time revealed the effects and regulatory mechanism of miR-296-5p in cardiac hypertrophy in vitro . We found suppressed expression of miR-129-5p and elevated expression of keap-1 in Ang II-induced cardiomyocyte hypertrophy model. MiR-129-5p mimic effectively suppressed Ang II-induced hypertrophic responses and oxidative stress. Further experiments showed that keap-1 is a target of miR-129-5p, and miR-129-5p inhibitor promoted cardiomyocyte hypertrophy and oxidative stress by elevating keap-1. Besides, si-keap-1 mediated the activation of Nrf2 pathway, while miR-129-5p inhibitor inactivated the Nrf2 pathway by further elevating keap-1. Conclusions: MiR-129-5p mimic protects against Ang II induced cardiomyocyte hypertrophy via activating Nrf2 pathway by targeting keap-1.

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Oxidative Stress and Cardiac Remodeling: An Updated Edge

Cited by 97 publications

References 50 publications

Caloric restriction reverses left ventricular hypertrophy through the regulation of cardiac iron homeostasis in impaired leptin signaling mice

Caloric restriction reverses left ventricular hypertrophy through the regulation of cardiac iron homeostasis in impaired leptin signaling mice

Oxidative Stress in Cardiovascular Diseases

MicroRNA-129-5p targets keap-1 to protect against cardiomyocyte hypertrophy via Nrf2 pathway

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