Rosuvastatin Attenuates Atrial Structural Remodelling in Rats with Myocardial Infarction through the Inhibition of the p38 MAPK Signalling Pathway

Wang, Mengzan; Li, Zhiyuan; Zhang, Xiao­hong; Xie, Xide; Zhang, Yujiao; Wang, Ximin; Hou, Yongyong

doi:10.1016/j.hlc.2014.11.012

Cited by 14 publications

(6 citation statements)

References 29 publications

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“…Therefore, the expression or activation of TAK1 is an important indicator of the activity of the TGF-β-TAK1-p38MAPK signaling pathway. Several studies have suggested that the p38MAPK pathway is activated in the MI model (5,16) and p38MAPK has become a therapeutic target for heart diseases (17,18). However, other studies have demonstrated the pro-survival function of p38MAPK in MI (19,20).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of p38MAPK potentiates mesenchymal stem cell therapy against myocardial infarction injury in rats

Zhang

Zhou

Mei

et al. 2017

Molecular Medicine Reports

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The present study aimed to investigate the protective effect of mesenchymal stem cell (MSC) therapy in combination with p38 mitogen‑activated protein (MAPK) inhibition against myocardial infarction (MI) injury in rats, and to elucidate the underlying mechanisms. An MI model was established by ligation of the anterior descending branch of the left coronary artery. The rats were divided into four groups: MSC transplantation, p38MAPK inhibitor (SB203580), MSC + SB203580 and model control group. HE staining and a TUNEL assay were performed to evaluate pathological changes and apoptosis. The expression levels of p38MAPK and transforming growth factor β‑activated kinase 1 (TAK1) were determined using reverse transcription‑polymerase chain reaction and western blot analyses. As shown by HE staining, classical morphological changes, including irregular cell arrangement and inflammatory infiltration were observed in the model rats, whereas MSC therapy or injection of the p38MAPK inhibitor ameliorated these pathological changes. Of note, the combined application of MSCs with the p38MAPK inhibitor exerted additive effects. The TUNEL assay showed that the combined application of MSCs with p38MAPK inhibitor also led to potentiation of effects, compared with either MSCs therapy or p38MAPK inhibitor injection alone. Mechanistically, the combined application of MSCs with p38MAPK inhibitor decreased the expression levels of TAK1 and p38MAPK at the mRNA and protein levels. In conclusion, p38MAPK inhibition potentiated the protective effects of MSCs therapy against MI in rats.

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Section: Discussionmentioning

confidence: 99%

Inhibition of p38MAPK potentiates mesenchymal stem cell therapy against myocardial infarction injury in rats

Zhang

Zhou

Mei

et al. 2017

Molecular Medicine Reports

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“…The profibrotic effect of p38α was confirmed by conditional p38α deletion in myofibroblasts, which demonstrated that a lack of p38α blocks cardiac fibroblast differentiation into myofibroblasts, reducing fibrosis in response to ischemic injury [ 74 ]. p38 pathway activation by MKK6 overexpression results in interstitial and perivascular cardiac fibrosis [ 74 ], and p38 inhibition may underlie the beneficial effects of some statins on cardiac remodeling after myocardial infarction [ 75 , 76 ]. Supporting this idea, protease inhibitors induce cardioprotection in models of ischemia–reperfusion, in part by attenuating p38 phosphorylation, leading to reductions in injury, ROS levels, and infarct size [ 77 ].…”

Section: P38 In Ischemia–reperfusion Injurymentioning

confidence: 99%

p38 MAPK Pathway in the Heart: New Insights in Health and Disease

Romero-Becerra

Santamans

Folgueira

et al. 2020

IJMS

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The p38 mitogen-activated kinase (MAPK) family controls cell adaptation to stress stimuli. p38 function has been studied in depth in relation to cardiac development and function. The first isoform demonstrated to play an important role in cardiac development was p38α; however, all p38 family members are now known to collaborate in different aspects of cardiomyocyte differentiation and growth. p38 family members have been proposed to have protective and deleterious actions in the stressed myocardium, with the outcome of their action in part dependent on the model system under study and the identity of the activated p38 family member. Most studies to date have been performed with inhibitors that are not isoform-specific, and, consequently, knowledge remains very limited about how the different p38s control cardiac physiology and respond to cardiac stress. In this review, we summarize the current understanding of the role of the p38 pathway in cardiac physiology and discuss recent advances in the field.

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“…Statins are commonly used in patients with obesity and type 2 diabetes to prevent atherosclerotic events, but they have striking effects in lessening epicardial adipocyte mass and inflammation, and thereby preventing fibrosis in the underlying myocardium . This anti‐inflammatory action may explain why statins ameliorate the development of an atrial myopathy in experimentally induced cardiac stress and in patients with AF . In randomized controlled trials (RCTs), statins reduced the incidence of new‐onset as well as recurrent AF; their use is also associated with a decrease in AF‐related thromboembolic events .…”

Section: Therapeutic Challenges In Patients With a Metabolic Disordermentioning

confidence: 99%

“…102,103 This anti-inflammatory action may explain why statins ameliorate the development of an atrial myopathy in experimentally induced cardiac stress and in patients with AF. [104][105][106] In randomized controlled trials (RCTs), statins reduced the incidence of new-onset as well as recurrent AF; 107-109 their use is also associated with a decrease in AF-related thromboembolic events. 110,111 At the same time, the use of statins is followed by an improvement in abnormal diastolic filling dynamics [112][113][114] as well as by reduced risk for new-onset HF with the features of HFpEF.…”

Section: Statinsmentioning

confidence: 99%

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Packer

2019

European J of Heart Fail

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Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk‐to‐benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post‐ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.

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Rosuvastatin Attenuates Atrial Structural Remodelling in Rats with Myocardial Infarction through the Inhibition of the p38 MAPK Signalling Pathway

Cited by 14 publications

References 29 publications

Inhibition of p38MAPK potentiates mesenchymal stem cell therapy against myocardial infarction injury in rats

Inhibition of p38MAPK potentiates mesenchymal stem cell therapy against myocardial infarction injury in rats

p38 MAPK Pathway in the Heart: New Insights in Health and Disease

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

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