p38 MAP kinases in the heart

Yokota, Tomohiro; Wang, Yibin

doi:10.1016/j.gene.2015.09.030

Cited by 116 publications

(102 citation statements)

References 96 publications

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“…Interestingly, both FOXO1 and MAPK14—another important node in our network—were also implicated in the development of heart failure [35, 36], therefore the identified targets may reflect key regulating mechanisms in both atherosclerotic disease and heart failure.…”

Section: Discussionmentioning

confidence: 99%

Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations

et al. 2017

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ObjectiveCirculating microRNAs (miRNAs) have been implicated in both heart failure and atherosclerotic disease. The aim of this study was to examine associations between heart failure specific circulating miRNAs, atherosclerotic disease and cardiovascular-related outcome in patients with heart failure.MethodsThe levels of 11 heart failure-specific circulating miRNAs were compared in plasma of 114 heart failure patients with and without different manifestations of atherosclerotic disease. We then studied these miRNAs in relation to biomarkers associated to atherosclerosis and to cardiovascular-related rehospitalizations during 18 months of follow-up.ResultsAt least one manifestation of atherosclerotic disease was found in 70 (61%) of the heart failure patients. A consistent trend was found between an increasing number of manifestations of atherosclerosis (peripheral arterial disease in specific), and lower levels of miR-18a-5p, miR-27a-3p, miR-199a-3p, miR-223-3p and miR-652-3p (all P < 0.05). Target prediction and network analyses identified several interactions between miRNA targets and biomarkers related to inflammation, angiogenesis and endothelial dysfunction. Lower miRNA levels were associated with higher levels of these atherosclerosis-related biomarkers. In addition, lower miRNA levels were significantly associated with rehospitalizations due to cardiovascular causes within 18 months, with let-7i-5p as strongest predictor [HR 2.06 (95% CI 1.29–3.28), C-index 0.70, P = 0.002].ConclusionsA consistent pattern of lower levels of circulating miRNAs was found in heart failure patients with atherosclerotic disease, in particular peripheral arterial disease. In addition, lower levels of miRNAs were associated with higher levels of biomarkers involved in atherosclerosis and an increased risk of a cardiovascular-related rehospitalization.Electronic supplementary materialThe online version of this article (doi:10.1007/s00392-017-1096-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations

et al. 2017

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“…We have previously reported that E2-activated p38β significantly reduces mitochondrial ROS after H/R and that a mitochondrial pool of p38β exists that interacts with MnSOD in NRCM [16, 17]. p38β belongs to the p38 MAPK family, which includes p38α, p38β, p38γ, and p38δ [39]. Of the four, the first two are expressed predominantly in the heart [40].…”

Section: Discussionmentioning

confidence: 99%

Estrogen Protects the Female Heart from Ischemia/Reperfusion Injury through Manganese Superoxide Dismutase Phosphorylation by Mitochondrial p38β at Threonine 79 and Serine 106

2016

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A collective body of evidence indicates that estrogen protects the heart from myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism remains incompletely understood. We have previously delineated a novel mechanism of how 17β-estradiol (E2) protects cultured neonatal rat cardiomyocytes from hypoxia/reoxygenation (H/R) by identifying a functionally active mitochondrial pool of p38β and E2-driven upregulation of manganese superoxide dismutase (MnSOD) activity via p38β, leading to the suppression of reactive oxygen species (ROS) and apoptosis. Here we investigate these cytoprotective actions of E2 in vivo. Left coronary artery ligation and reperfusion was used to produce I/R injury in ovariectomized (OVX) female mice and in estrogen receptor (ER) null female mice. E2 treatment in OVX mice reduced the left ventricular infarct size accompanied by increased activity of mitochondrial p38β and MnSOD. I/R-induced infarct size in ERα knockout (ERKO), ERβ knockout (BERKO) and ERα and β double knockout (DERKO) female mice was larger than that in wild type (WT) mice, with little difference among ERKO, BERKO, and DERKO. Loss of both ERα and ERβ led to reduced activity of mitochondrial p38β and MnSOD at baseline and after I/R. The physical interaction between mitochondrial p38β and MnSOD in the heart was detected by co-immunoprecipitation (co-IP). Threonine 79 (T79) and serine 106 (S106) of MnSOD were identified to be phosphorylated by p38β in kinase assays. Overexpression of WT MnSOD in cardiomyocytes reduced ROS generation during H/R, while point mutation of T79 and S106 of MnSOD to alanine abolished its antioxidative function. We conclude that the protective effects of E2 and ER against cardiac I/R injury involve the regulation of MnSOD via posttranslational modification of the dismutase by p38β.

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“…By secreting cytokines and chemokines, positive effects on cancer cells (11,(16)(17)(18)(19)(20). p38 acts as a regulator in inflammation but as a suppressor in tumors.…”

Section: The Tumor Microenvironment and Cancermentioning

confidence: 99%

“…p38 acts as a regulator in inflammation but as a suppressor in tumors. p38α, a prototypic p38 MAPK, was originally identified as an essential signaling kinase for the production of many inflammatory cytokines (16). p38 inactivation supports cell transformation in vitro and promotes experimental cancer development in vivo.…”

Section: The Tumor Microenvironment and Cancermentioning

confidence: 99%

Yin-yang regulating effects of cancer-associated genes, proteins, and cells: An ancient Chinese concept in vogue in modern cancer research

Wei

2017

BST

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p38 MAP kinases in the heart

Cited by 116 publications

References 96 publications

Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations

Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations

Estrogen Protects the Female Heart from Ischemia/Reperfusion Injury through Manganese Superoxide Dismutase Phosphorylation by Mitochondrial p38β at Threonine 79 and Serine 106

Yin-yang regulating effects of cancer-associated genes, proteins, and cells: An ancient Chinese concept in vogue in modern cancer research

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