Effect of Targeting Mitogen-Activated Protein Kinase on Cardiac Remodeling in Rats

Baraka, Azza; Mikhail, M.N.; Guemei, Aida A.; Ghotny, Samar El

doi:10.1177/1074248409349620

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…For instance, in the heart, atorvastatin increases phosphorylation of a host of mediators associated with NO signalling, such as ERK, PDK‐1, Akt and eNOS itself, plausibly via an adenosine receptor‐dependent mechanism (Merla et al ., ; Ye et al ., ). Direct modulation of NO signalling by statins downstream of NOS was also suggested by another study, where rosuvastatin administration reverted the elevation in mean arterial blood pressure and cardiac remodelling caused by a treatment with a NOS inhibitor, L‐NAME (Baraka et al ., ). Statins modulate cardiac NO metabolism under hyperlipidaemic conditions as well.…”

Section: Interaction Of Pharmacological Treatment Of Metabolic Syndromentioning

confidence: 97%

CardiacNOsignalling in the metabolic syndrome

Pecháňová

Varga

Cebová

et al. 2014

British J Pharmacology

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It is well documented that metabolic syndrome (i.e. a group of risk factors, such as abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides and low cholesterol level in high-density lipoprotein), which raises the risk for heart disease and diabetes, is associated with increased reactive oxygen and nitrogen species (ROS/RNS) generation. ROS/RNS can modulate cardiac NO signalling and trigger various adaptive changes in NOS and antioxidant enzyme expressions/activities. While initially these changes may represent protective mechanisms in metabolic syndrome, later with more prolonged oxidative, nitrosative and nitrative stress, these are often exhausted, eventually favouring myocardial RNS generation and decreased NO bioavailability. The increased oxidative and nitrative stress also impairs the NO-soluble guanylate cyclase (sGC) signalling pathway, limiting the ability of NO to exert its fundamental signalling roles in the heart. Enhanced ROS/RNS generation in the presence of risk factors also facilitates activation of redox-dependent transcriptional factors such as NF-κB, promoting myocardial expression of various pro-inflammatory mediators, and eventually the development of cardiac dysfunction and remodelling. While the dysregulation of NO signalling may interfere with the therapeutic efficacy of conventional drugs used in the management of metabolic syndrome, the modulation of NO signalling may also be responsible for the therapeutic benefits of already proven or recently developed treatment approaches, such as ACE inhibitors, certain β-blockers, and sGC activators. Better understanding of the above-mentioned pathological processes may ultimately lead to more successful therapeutic approaches to overcome metabolic syndrome and its pathological consequences in cardiac NO signalling. LINKED ARTICLESThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi. org/10.1111/bph.2015.172.issue-6 Abbreviations ADMA, asymmetric dimethylarginine; AF, atrial fibrillation; DPP-4, dipeptidyl peptidase-4; PARP-1, poly [ADP-ribose] polymerase-1; PETN, pentaerythrityl tetranitrate; PKG, cGMP-dependent PK; ROCK, Rho-associated PK; ROS, reactive oxygen species; SNO, S-nitrosothiol; Tempol, 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl; 15D-PGJ2, 15-deoxy-Δ IntroductionAlthough NO was discovered decades ago, scientific interest in this gasotransmitter is continuously increasing. Enzymic and non-enzymic formation of NO and cGMP-dependent and independent NO signalling has been reviewed in detail in the current Themed Issue (Csonka et al., 2015) and elsewhere (Ferdinandy and Schulz, 2003;Stasch et al., 2011;Tang et al., 2013;Rassaf et al., 2014). Intercellular and intracellular NO signalling is very complex, reflecting its many pathways and interactions with other free radicals to form additional signalling molecules. Reactive oxygen species (ROS), especially the superoxide anion radical, can reac...

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Section: Interaction Of Pharmacological Treatment Of Metabolic Syndromentioning

confidence: 97%

CardiacNOsignalling in the metabolic syndrome

Pecháňová

Varga

Cebová

et al. 2014

British J Pharmacology

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“…Previous studies have shown that patients with obesity display increased levels of C-reactive protein (CRP) and IL-6 compared to the controls (Ellulu et al, 2016;Okamoto et al, 2015). In addition, the activation of p38MAPK has been correlated with myocardial remodeling (Yoshida et al, 2001;Baraka et al, 2009;Yu et al, 2012). p38MAPK can be activated by a variety of stimuli, such as elevated levels of free fatty acids, cholesterol, glucose, and proinflammatory mediators (Ragheb et al, 2009;Shalini et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…p38MAPK can be activated by a variety of stimuli, such as elevated levels of free fatty acids, cholesterol, glucose, and proinflammatory mediators (Ragheb et al, 2009;Shalini et al, 2016). Moreover, the activation of p38MAPK can regulate gene expression, which may promote myocardial remodeling (Baraka et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Ezetimibe prevents myocardial remodeling in an obese rat model by inhibiting inflammation

Zhao

Chang

et al. 2018

Acta Biochim Pol

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Inflammation plays an important role in the development of many obesity-related diseases. This study aimed to investigate the effect of ezetimibe on inflammation and myocardial remodeling in obese rats. A rat model of obesity was established, and myocardial damage was examined by transmission electron microscopy and Masson staining. Twenty obese rats were divided into two groups (n=10): obese group and ezetimibe group. Ten SD rats were used as controls. Western blot was performed to monitor the expression of P-p38MAPK and interleukin (IL)-6. Immunohistochemical staining was used to monitor the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. In the obese rats group, we observed increased inflammatory factors and myocardial hypertrophy. In contrast, the ezetimibe group exhibited decreased expression of inflammatory factors and an improvement in myocardial remodeling compared to the obese group. Mechanistically, we found that ezetimibe decreased P-p38MAPK, IL-6, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 levels in the hearts of the obese rats. Taken together, these results indicate that ezetimibe may improve myocardial remodeling in obese rats by inhibiting inflammation.

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Rosuvastatin Alleviates Diabetic Cardiomyopathy by Inhibiting NLRP3 Inflammasome and MAPK Pathways in a Type 2 Diabetes Rat Model

Luo

Wang

et al. 2013

Cardiovasc Drugs Ther

128

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Effect of Targeting Mitogen-Activated Protein Kinase on Cardiac Remodeling in Rats

Abstract: Targeting MAPK might represent a useful therapeutic avenue to ameliorate cardiac remodeling and support the notion that atRA and statins are potential candidates for the prevention and therapy of cardiac remodeling.

Cited by 6 publications

References 35 publications

CardiacNOsignalling in the metabolic syndrome

CardiacNOsignalling in the metabolic syndrome

Ezetimibe prevents myocardial remodeling in an obese rat model by inhibiting inflammation

Rosuvastatin Alleviates Diabetic Cardiomyopathy by Inhibiting NLRP3 Inflammasome and MAPK Pathways in a Type 2 Diabetes Rat Model

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