MAP Kinase Phosphatase-5 Deficiency Protects Against Pressure Overload-Induced Cardiac Fibrosis

Zhong, Chao; Min, Kisuk; Zhao, Zhiqiang; Zhang, Cheng; Gao, Erhe; Huang, Yan; Zhang, Xinbo; Baldini, Margaret; Roy, Rajika; Yang, Xiaofeng; Koch, Walter J.; Bennett, Anton M.

doi:10.3389/fimmu.2021.790511

Cited by 16 publications

(10 citation statements)

References 66 publications

(138 reference statements)

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“…These sections were then incubated with a graded ethanol series for deparaffinization and hydration. Heart sections were stained with Masson’s trichrome (Sigma-Aldrich) to visualize myocardial fibrosis, hematoxylin, and eosin (H&E) (Sigma-Aldrich) to show the heart structure, as previously described ( 23 , 24 ). For immunohistochemistry, sections were incubated with anti-CD45 (Abcam), anti-CD68 (Abcam), and anti-CD31 (Abcam) primary antibodies, followed by biotin-conjugated secondary antibodies (Embime).…”

Section: Methodsmentioning

confidence: 99%

Edgeworthia gardneri (Wall.) Meisn. extract protects against myocardial infarction by inhibiting NF-κB-and MAPK-mediated endothelial inflammation

Wei

Tang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundExperimental and clinical evidence has demonstrated a pivotal role of inflammation in the pathogenesis of ischemic heart disease, and targeting inflammation has been shown to provide clinical benefits for patients with coronary disease. Endothelial cells constitute the majority of non-cardiomyocytes in the heart. Endothelial pro-inflammatory activation is recognized as a critical component in the pathophysiology of cardiovascular disease. The dried flowers of Edgeworthia gardneri (Wall.) Meisn. (EG) have been widely used as Tibetan folk medicine to ameliorate a range of metabolic disorders, such as diabetes mellitus, hyperlipidemia, hypertension, and obesity. However, its role in modulating endothelial inflammation and ischemic heart disease has not been evaluated.Methods and resultsHerein, using a preclinical rat model of coronary artery ligation-induced myocardial infarction (MI), we demonstrated that systemic administration of EG extract (EEEG) attenuated ischemic cardiac injury. EEEG reduced myocardial infarct size, improved cardiac function, and ameliorated adverse cardiac remodeling. Moreover, the cardioprotective effects of EEEG were associated with decreased MI-induced myocardial inflammation. Consistent with the anti-inflammatory role of EEEG in vivo, EEEG attenuated TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) activation and monocyte-endothelial cell firm adhesion in vitro. Mechanistically, our data showed that EEEG’s mode of action suppresses the activation of NF-κB, ERK, and p38 MAPK signaling pathways in ECs. Importantly, we demonstrated that EEEG inhibits endothelial inflammation in an NF-κB- and p38 MAPK-dependent manner using pharmacological inhibitors.ConclusionCollectively, this study identified EG as a potential therapeutic agent in attenuating endothelial inflammation and managing ischemic cardiovascular disease.

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Section: Methodsmentioning

confidence: 99%

Edgeworthia gardneri (Wall.) Meisn. extract protects against myocardial infarction by inhibiting NF-κB-and MAPK-mediated endothelial inflammation

Wei

Tang

et al. 2022

Front. Cardiovasc. Med.

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“…However, in nonischemic heart failure, IL-33 was cardioprotective against remodeling due to mechanical stress [280]. IL-4 was also implicated as a contributor to cardiac fibrosis [281], as it promoted pro-fibrotic activity in macrophages [282], and IL-17 upregulated remodeling pathways in human cardiac fibroblasts as well as in heart failure in mice [283,284].…”

Section: Cardiac Fibrosismentioning

confidence: 99%

The Role of Pro-Inflammatory Cytokines in the Pathogenesis of Cardiovascular Disease

Zhang,

Dhalla

2024

IJMS

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With cardiovascular disease (CVD) being a primary source of global morbidity and mortality, it is crucial that we understand the molecular pathophysiological mechanisms at play. Recently, numerous pro-inflammatory cytokines have been linked to several different CVDs, which are now often considered an adversely pro-inflammatory state. These cytokines most notably include interleukin-6 (IL-6),tumor necrosis factor (TNF)α, and the interleukin-1 (IL-1) family, amongst others. Not only does inflammation have intricate and complex interactions with pathophysiological processes such as oxidative stress and calcium mishandling, but it also plays a role in the balance between tissue repair and destruction. In this regard, pre-clinical and clinical evidence has clearly demonstrated the involvement and dynamic nature of pro-inflammatory cytokines in many heart conditions; however, the clinical utility of the findings so far remains unclear. Whether these cytokines can serve as markers or risk predictors of disease states or act as potential therapeutic targets, further extensive research is needed to fully understand the complex network of interactions that these molecules encompass in the context of heart disease. This review will highlight the significant advances in our understanding of the contributions of pro-inflammatory cytokines in CVDs, including ischemic heart disease (atherosclerosis, thrombosis, acute myocardial infarction, and ischemia-reperfusion injury), cardiac remodeling (hypertension, cardiac hypertrophy, cardiac fibrosis, cardiac apoptosis, and heart failure), different cardiomyopathies as well as ventricular arrhythmias and atrial fibrillation. In addition, this article is focused on discussing the shortcomings in both pathological and therapeutic aspects of pro-inflammatory cytokines in CVD that still need to be addressed by future studies.

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“…Interleukin-33 (IL-33) has been associated with pro-fibrotic signaling in rats with MI and in individuals diagnosed with HF. IL-4 has been identified as a contributor to heart fibrosis, as it stimulates pro-fibrotic activity in macrophages [ 58 , 59 , 60 ].…”

Section: Inflammatory Factorsmentioning

confidence: 99%

Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications

Tudurachi,

Anghel,

Tudurachi

et al. 2024

Biomedicines

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Myocardial infarction (MI) often leads to heart failure (HF) through acute or chronic maladaptive remodeling processes. This establishes coronary artery disease (CAD) and HF as significant contributors to cardiovascular illness and death. Therefore, treatment strategies for patients with CAD primarily focus on preventing MI and lessening the impact of HF after an MI event. Myocardial fibrosis, characterized by abnormal extracellular matrix (ECM) deposition, is central to cardiac remodeling. Understanding these processes is key to identifying new treatment targets. Recent studies highlight SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RAs) as favorable options in managing type 2 diabetes due to their low hypoglycemic risk and cardiovascular benefits. This review explores inflammation’s role in cardiac fibrosis and evaluates emerging anti-diabetic medications’ effectiveness, such as SGLT2i, GLP1-RAs, and dipeptidyl peptidase-4 inhibitors (DPP4i), in preventing fibrosis in patients with diabetes post-acute MI. Recent studies were analyzed to identify effective medications in reducing fibrosis risk in these patients. By addressing these areas, we can advance our understanding of the potential benefits of anti-diabetic medications in reducing cardiac fibrosis post-MI and improve patient outcomes in individuals with diabetes at risk of HF.

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MAP Kinase Phosphatase-5 Deficiency Protects Against Pressure Overload-Induced Cardiac Fibrosis

Cited by 16 publications

References 66 publications

Edgeworthia gardneri (Wall.) Meisn. extract protects against myocardial infarction by inhibiting NF-κB-and MAPK-mediated endothelial inflammation

Edgeworthia gardneri (Wall.) Meisn. extract protects against myocardial infarction by inhibiting NF-κB-and MAPK-mediated endothelial inflammation

The Role of Pro-Inflammatory Cytokines in the Pathogenesis of Cardiovascular Disease

Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications

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