scholarly journals Sleeve Gastrectomy Ameliorates Diabetes-Induced Cardiac Hypertrophy Correlates With the MAPK Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Xu ◽  
Huanxin Ding ◽  
Songhan Li ◽  
Shuohui Dong ◽  
Linchuan Li ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Cardiac Hypertrophy ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Sham Group ◽  
Heart Function ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Metabolic Parameters ◽  
Myocardial Glucose Uptake

Background: Cardiac hypertrophy as a main pathological manifestation of diabetic cardiomyopathy (DCM), is a significant complication of diabetes. Bariatric surgery has been proven to relieve DCM; however, whether it can alleviate diabetes-induced cardiac hypertrophy is undefined.Methods: Diabetic and obese rats were performed sleeve gastrectomy (SG) after having diabetes for 16weeks. The rats were euthanized 8weeks after SG. Metabolic parameters, heart function parameters, myocardial glucose uptake, morphometric and histological changes, and the expression level of mitogen-activated protein kinases (MAPKs) were determined and compared among the control group (CON group), diabetes mellitus group (DM group), sham operation group (SHAM group), and SG group.Results: Compared with the SHAM group, the blood glucose, body weight, insulin resistance, and other metabolic parameters were significantly improved in the SG group. There was also a marked improvement in myocardial morphometric and histological parameters after SG. Furthermore, the myocardial glucose uptake and heart function were reversed after SG. Additionally, the phosphorylation of MAPKs was inhibited after SG, including p38 MAPKs, c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases 1/2 (ERK1/2). The expression of DUSP6, which dephosphorylates ERK1/2, was upregulated after SG. These findings suggest that SG ameliorated diabetes-induced cardiac hypertrophy correlates with the MAPK signaling pathway.Conclusion: These results showed that diabetes-induced cardiac hypertrophy was ameliorated after SG was closely related to the inhibition of the MAPK signaling pathway and upregulation of DUSP6. Therefore, this study provides a novel strategy for treating diabetes-induced cardiac hypertrophy.

scholarly journals The role of the Grb2–p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis

2003 ◽  
Vol 111 (6) ◽  
pp. 833-841 ◽  
Author(s):  
Shaosong Zhang ◽  
Carla Weinheimer ◽  
Michael Courtois ◽  
Attila Kovacs ◽  
Cindy E. Zhang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

AMPK activation enhances PPARα activity to inhibit cardiac hypertrophy via ERK1/2 MAPK signaling pathway

2011 ◽  
Vol 511 (1-2) ◽  
pp. 1-7 ◽  
Author(s):  
Rongsen Meng ◽  
Zhaohui Pei ◽  
Aixia Zhang ◽  
Yutian Zhou ◽  
Xingming Cai ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Ampk Activation

scholarly journals Prostaglandin E1 attenuates AngII-induced cardiac hypertrophy via EP3 receptor activation and Netrin-1upregulation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Shen ◽  
Y Shen ◽  
X Wang ◽  
B He
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Prostaglandin E1 ◽  
Receptor Activation ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy ◽  
Ep3 Receptor

Abstract Aims Pathological cardiac hypertrophy induced by activation of the renin–angiotensin–aldosterone system (RAAS) is one of the leading causes of heart failure. However, in current clinical practice, the strategy for targeting the RAAS is not sufficient to reverse hypertrophy. Here, we investigated the effect of prostaglandin E1 (PGE1) on angiotensin II (AngII)-induced cardiac hypertrophy and potential molecular mechanisms underlying the effect. Methods and results Adult male C57 mice were continuously infused with AngII or saline and treated daily with PGE1 or vehicle for two weeks. Neonatal rat cardiomyocytes were cultured to detect AngII-induced hypertrophic responses. We found that PGE1 ameliorated AngII-induced cardiac hypertrophy both in vivo and in vitro. The RNA sequencing (RNA-seq) and expression pattern analysis results suggest that Netrin-1 (Ntn1) is the specific target gene of PGE1. The protective effect of PGE1 was eliminated after knockdown of Ntn1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the PGE1-mediated signaling pathway changes are associated with the mitogen-activated protein kinase (MAPK) pathway. PGE1 suppressed AngII-induced activation of the MAPK signaling pathway, and such an effect was attenuated by Ntn1 knockdown. Blockade of MAPK signaling rescued the phenotype of cardiomyocytes caused by Ntn1 knockdown, indicating that MAPK signaling may act as the downstream effector of Ntn1. Furthermore, inhibition of the E prostanoid (EP)3 receptor, as opposed to the EP1, EP2, or EP4 receptor, in cardiomyocytes reversed the effect of PGE1, and activation of EP3 by sulprostone, a specific agonist, mimicked the effect of PGE1. Conclusion In conclusion, PGE1 ameliorates AngII-induced cardiac hypertrophy through activation of the EP3 receptor and upregulation of Ntn1, which inhibits the downstream MAPK signaling pathway. Thus, targeting EP3, as well as the Ntn1–MAPK axis, may represent a novel approach for treating pathological cardiac hypertrophy. FUNDunding Acknowledgement Type of funding sources: None.

Kaempferol Attenuates Cardiac Hypertrophy via Regulation of ASK1/MAPK Signaling Pathway and Oxidative Stress

Planta Medica ◽  
2017 ◽  
Vol 83 (10) ◽  
pp. 837-845 ◽  
Author(s):  
Hong Feng ◽  
Jianlei Cao ◽  
Guangyu Zhang ◽  
Yanggan Wang
Keyword(s):  
Oxidative Stress ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
In Vitro Study ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mouse Heart ◽  
H9c2 Cardiomyocytes

AbstractKaempferol has been demonstrated to provide benefits for the treatment of atherosclerosis, coronary heart disease, hyperlipidemia, and diabetes through its antioxidant and anti-inflammatory properties. However, its role in cardiac hypertrophy remains to be elucidated. The aim of our study was to investigate the effects of kaempferol on cardiac hypertrophy and the underlying mechanism. Mice subjected to aorta banding were treated with or without kaempferol (100 mg/kg/d, p. o.) for 6 weeks. Echocardiography was performed to evaluate cardiac function. Mice hearts were collected for pathological observation and molecular mechanism investigation. H9c2 cardiomyocytes were stimulated with or without phenylephrine for in vitro study. Kaempferol significantly attenuated cardiac hypertrophy induced by aorta banding as evidenced by decreased cardiomyocyte areas and interstitial fibrosis, accompanied with improved cardiac functions and decreased apoptosis. The ASK1/MAPK signaling pathways (JNK1/2 and p38) were markedly activated in the aorta banding mouse heart but inhibited by kaempferol treatment. In in vitro experiments, kaempferol also inhibited the activity of ASK1/JNK1/2/p38 signaling pathway and the enlargement of H9c2 cardiomyocytes. Furthermore, our study revealed that kaempferol could protect the mouse heart and H9c2 cells from pathological oxidative stress. Our investigation indicated that treatment with kaempferol protects against cardiac hypertrophy, and its cardioprotection may be partially explained by the inhibition of the ASK1/MAPK signaling pathway and the regulation of oxidative stress.

Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes

2007 ◽  
Vol 292 (5) ◽  
pp. E1325-E1332 ◽  
Author(s):  
Amélie Pelletier ◽  
Lise Coderre
Keyword(s):  
Oxidative Stress ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Chronic Exposure ◽  
Ketone Bodies ◽  
Metabolic Stress ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Altered Glucose

In aerobic conditions, the heart preferentially oxidizes fatty acids. However, during metabolic stress, glucose becomes the major energy source, and enhanced glucose uptake has a protective effect on heart function and cardiomyocyte survival. Thus abnormal regulation of glucose uptake may contribute to the development of cardiac disease in diabetics. Ketone bodies are often elevated in poorly controlled diabetics and are associated with increased cellular oxidative stress. Thus we sought to determine the effect of the ketone body β-hydroxybutyrate (OHB) on cardiac glucose uptake during metabolic stress. We used 2,4-dinitrophenol (DNP), an uncoupler of the mitochondrial oxidative chain, to mimic hypoxia in cardiomyocytes. Our data demonstrated that chronic exposure to OHB provoked a concentration-dependent decrease of DNP action, resulting in 56% inhibition of DNP-mediated glucose uptake at 5 mM OHB. This was paralleled by a diminution of DNP-mediated AMP-activated protein kinase (AMPK) and p38 MAPK phosphorylation. Chronic exposure to OHB also increased reactive oxygen species (ROS) production by 1.9-fold compared with control cells. To further understand the role of ROS in OHB action, cardiomyocytes were incubated with H2O2. Our results demonstrated that this treatment diminished DNP-induced glucose uptake without altering activation of the AMPK/p38 MAPK signaling pathway. Incubation with the antioxidant N-acetylcysteine partially restored DNP-mediated glucose but not AMPK/p38 MAPK activation. In conclusion, these results suggest that ketone bodies, through inhibition of the AMPK/p38 MAPK signaling pathway and ROS overproduction, regulate DNP action and thus cardiac glucose uptake. Altered glucose uptake in hyperketonemic states during metabolic stress may contribute to diabetic cardiomyopathy.

scholarly journals Delphinidin attenuates pathological cardiac hypertrophy via the AMPK/NOX/MAPK signaling pathway

Aging ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 5362-5383 ◽  
Author(s):  
Youming Chen ◽  
Zhuowang Ge ◽  
Shixing Huang ◽  
Lei Zhou ◽  
Changlin Zhai ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Pathological Cardiac Hypertrophy

MAPK: A Key Player in the Development and Progression of Stroke

2020 ◽  
Vol 19 (4) ◽  
pp. 248-256
Author(s):  
Yangmin Zheng ◽  
Ziping Han ◽  
Haiping Zhao ◽  
Yumin Luo
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Complex Disease ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Effective Prevention ◽  
Prevention And Treatment ◽  
Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

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