scholarly journals Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway

2015 ◽  
Vol 36 (3) ◽  
pp. 323-333 ◽  
Author(s):  
Zhong-wei Liu ◽  
Jun-kui Wang ◽  
Chuan Qiu ◽  
Gong-chang Guan ◽  
Xin-hong Liu ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy

Kir6.1 improves cardiac dysfunction in diabetic cardiomyopathy via the AKT-Foxo1 signaling pathway

2020 ◽  
Author(s):  
Jinxin Wang ◽  
Jing Bai ◽  
Peng Duan ◽  
Hao Wang ◽  
Yang Li ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Diabetic Patients ◽  
Protein Levels ◽  
Inwardly Rectifying Potassium Channel ◽  
Transmission Electron ◽  
Hematoxylin And Eosin ◽  
And Function

Abstract Background: Diabetic cardiomyopathy (DCM) severely impairs the health of diabetic patients. Previous studies have shown that the expression of inwardly rectifying potassium channel 6.1 (Kir6.1) in heart mitochondria is significantly reduced in type 1 diabetes. However, whether its expression and function are changed and what role it plays in type 2 DCM have not been reported. This study investigated the role and mechanism of Kir6.1 in DCM.Methods: The cardiac function in mice was analyzed by echocardiography, ELISA, hematoxylin and eosin staining, TUNEL and transmission electron microscopy. The mitochondrial function in cardiomyocytes was measured by the oxygen consumption rate and the mitochondrial membrane potential (ΔΨm). Kir6.1 expression at the mRNA and protein levels was analyzed by quantitative real-time PCR and western blotting (WB), respectively. The protein expression of t-AKT, p-AKT, t-Foxo1, and p-Foxo1 was analyzed by WB.Results: We found that the cardiac function and the Kir6.1 expression in DCM mice were decreased. Kir6.1 overexpression improved cardiac dysfunction and upregulated the phosphorylation of AKT and Foxo1 in the DCM mouse model. Furthermore, Kir6.1 overexpression also improved cardiomyocyte dysfunction and upregulated the phosphorylation of AKT and Foxo1 in cardiomyocytes with insulin resistance. In contrast, cardiac-specific Kir6.1 knockout aggravated the cardiac dysfunction and downregulated the phosphorylation of AKT and Foxo1 in DCM mice. Furthermore, Foxo1 activation downregulated the expression of Kir6.1 and decreased the ΔΨm in cardiomyocytes. In contrast, Foxo1 inactivation upregulated the expression of Kir6.1 and increased the ΔΨm in cardiomyocytes. Chromatin immunoprecipitation assay demonstrated that the Kir6.1 promoter region contains a functional Foxo1-binding site .Conclusions: Kir6.1 improves cardiac dysfunction in DCM, probably through the AKT-Foxo1 signaling pathway. Moreover, the crosstalk between Kir6.1 and the AKT-Foxo1 signaling pathway may provide new strategies for reversing the defective signaling in DCM.

The Effects of Carvedilol on Cardiac Function and the AKT/XIAP Signaling Pathway in Diabetic Cardiomyopathy Rats

Cardiology ◽  
2016 ◽  
Vol 136 (3) ◽  
pp. 204-211 ◽  
Author(s):  
Wencheng Zheng ◽  
Xiaoming Shang ◽  
Chunlai Zhang ◽  
Xiang Gao ◽  
Barry Robinson ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
Interstitial Fibrosis ◽  
High Energy ◽  
Control Group ◽  
Tunel Staining ◽  
Myocardial Inflammation ◽  
Western Blots ◽  
Male Wistar Rats

Objectives: Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction, myocardial inflammation, interstitial fibrosis and cardiomyocytes apoptosis. The present study aimed to investigate the effects of carvedilol on cardiac function and the AKT/XIAP signaling pathway in DCM rats. Methods: Male Wistar rats were randomly divided into 3 groups: the control group, diabetic mellitus (DM) group and DM with carvedilol treatment group. DM rats were induced by streptozotocin accompanied by high energy intake. Carvedilol was orally administered at a dose of 10 mg/kg/day. After 16 weeks, the interrelated blood data were detected by biochemical analysis. Cardiac function was evaluated by echocardiography and the serum NT-proBNP level. The changes of myocardium ultrastructural and fibrosis were determined by electron microscopy and Masson's staining. Apoptotic cells were examined by TUNEL staining and interrelated proteins were measured by immunohistochemical and Western blots. Results: Rats in the DM group showed significant serum elevation of glucose, cholesterol, triglyceride, NT-proBNP, IL-1β and TNF-α, along with decreased cardiac function. Moreover, in the DM group, the levels of myocardial apoptosis and fibrosis were all increased accompanied by upregulation of caspase-3 and downregulation of phos-AKT and phos-XIAP, whereas carvedilol treatment prevented or reversed all the changes without influencing plasma levels of glucose, cholesterol and triglyceride. Conclusions: The AKT/XIAP signaling pathway may be involved in DCM. Carvedilol can improve cardiac function, possibly not only by upregulating the AKT/XIAP antiapoptotic signaling pathway and subsequently attenuating myocardial fibrosis, but also through suppressing the myocardial inflammation response.

Abstract 317: Conditional Knockout Of Phd2 Ameliorates High-fat Diet-induced Cardiac Dysfunction Via Inhibition Of Tlr4-nfκB Pathway In A Hifa-independent Manner

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
heng Zeng ◽  
Jian-Xiong chen
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
Conditional Knockout ◽  
High Fat ◽  
Angiogenic Growth Factors ◽  
Independent Manner

Oxygen sensors prolyl hydroxylases (PHDs) plays an important role in the regulation of hypoxia-inducible factor (HIFα) as well as nuclear factor-κ B (NF-κB) activity. Our previous study demonstrated that activation of vascular Toll-like receptor TLR-MyD88-IRAK4 signaling pathway contributes to vascular dysfunction in high-fat-diet (HFD)-induced diabetes. The present study investigates whether conditional knockout of prolyl hydroxylase-2 (PHD2) improves cardiac function via suppression of TLR-NF-κb signaling in a HFD-induced diabetic cardiomyopathy mouse model. Wild type (WT-Cre + ), PHD2 conditional knockout (PHD2CKO) and PHD2 +/- mice were fed with either HFD or normal chow diet (NFD) for 18 weeks. The levels of PHD1-3, HIF, angiogenic growth factors, MyD88, IRAK-4, TLR4, NF-κb and Wnt7b gene expression were measured. Cardiac hypertrophy, fibrosis and cardiac function were analyzed at 18 weeks after PHD2 deactivation . Feeding of WT-Cre + mice with HFD for 18 weeks resulted in a significant reduction of cardiac functions. The basal expression of PHD2 was significantly increased in the heart of HFD mice. The expression of PHD2 was significantly reduced in the heart of PHD2CKO and PHD2 +/- mice fed with HFD whereas PHD1 and PHD3 expression remains unchanged. Conditional knockout of PHD2 resulted in suppression of MyD88, IRAK-4, TLR4, NF-κb and Wnt7b expression. Deactivation of PHD2 had little effect on the expression of HIF1α, HIF2α and angiogenic growth factor in the hearts of HFD-induced diabetic mice. Conditional knockout of PHD2 further suppressed HFD-induced cardiac hypertrophy and significantly improved HFD-induced cardiac dysfunction. In contrast, conditional knockout of PHD2 resulted in an increase in HIFα expression and cardiac dysfunction in NFD mice. These results suggest that deactivation of PHD2 attenuates HFD-induced diabetic cardiomyopathy via suppression of TLR4-MyD88-IRAK4-NF-κb-Wnt7b signaling pathway in a HIF-independent manner.

scholarly journals Identification and analysis of circulating long non-coding RNAs with high significance in diabetic cardiomyopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tarun Pant ◽  
Anuradha Dhanasekaran ◽  
Ming Zhao ◽  
Edward B. Thorp ◽  
Joseph M. Forbess ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Bioinformatic Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Diagnostic Biomarker ◽  
Diagnostic Biomarkers ◽  
Mitogen Activated Protein ◽  
Non Coding Rnas ◽  
Α Chain ◽  
Factor Α

AbstractDiabetic cardiomyopathy (DCM) lacks diagnostic biomarkers. Circulating long non-coding RNAs (lncRNAs) can serve as valuable diagnostic biomarkers in cardiovascular disease. To seek potential lncRNAs as a diagnostic biomarker for DCM, we investigated the genome-wide expression profiling of circulating lncRNAs and mRNAs in type 2 diabetic db/db mice with and without DCM and performed bioinformatic analyses of the deregulated lncRNA-mRNA co-expression network. Db/db mice had obesity and hyperglycemia with normal cardiac function at 6 weeks of age (diabetes without DCM) but with an impaired cardiac function at 20 weeks of age (DCM) on an isolated Langendorff apparatus. Compared with the age-matched controls, 152 circulating lncRNAs, 127 mRNAs and 3355 lncRNAs, 2580 mRNAs were deregulated in db/db mice without and with DCM, respectively. The lncRNA-mRNA co-expression network analysis showed that five deregulated lncRNAs, XLOC015617, AK035192, Gm10435, TCR-α chain, and MouselincRNA0135, have the maximum connections with differentially expressed mRNAs. Bioinformatic analysis revealed that these five lncRNAs were highly associated with the development and motion of myofilaments, regulation of inflammatory and immune responses, and apoptosis. This finding was validated by the ultrastructural examination of myocardial samples from the db/db mice with DCM using electron microscopy and changes in the expression of myocardial tumor necrosis factor-α and phosphorylated p38 mitogen-activated protein kinase in db/db mice with DCM. These results indicate that XLOC015617, AK035192, Gm10435, TCR-α chain, and MouselincRNA0135 are crucial circulating lncRNAs in the pathogenesis of DCM. These five circulating lncRNAs may have high potential as a diagnostic biomarker for DCM.

Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: Possible involvement of PKC–MAPK signaling pathway

2012 ◽  
Vol 47 (3) ◽  
pp. 604-614 ◽  
Author(s):  
Vivian Soetikno ◽  
Flori R. Sari ◽  
Vijayakumar Sukumaran ◽  
Arun Prasath Lakshmanan ◽  
Sayaka Mito ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
Mapk Signaling ◽  
Diabetic Rats ◽  
Mapk Signaling Pathway

scholarly journals 5213Manipulation of cardiac O-GlcNAc modification alters cardiac function and remodelling in the setting of diabetic cardiomyopathy

2018 ◽  
Vol 39 (suppl_1) ◽  
Author(s):  
D Prakoso ◽  
H Kiriazis ◽  
M Tate ◽  
H Qian ◽  
M Deo ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy

Rutin alleviates diabetic cardiomyopathy and improves cardiac function in diabetic ApoEknockout mice

2017 ◽  
Vol 814 ◽  
pp. 151-160 ◽  
Author(s):  
Ruo Huang ◽  
Zhendong Shi ◽  
Li Chen ◽  
Yanqun Zhang ◽  
Jing Li ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy

The Effect of Gypenosides on Cardiac Function and Expression of Cytoskeletal Genes of Myocardium in Diabetic Cardiomyopathy Rats

2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Diastolic Pressure ◽  
Pure Water ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Ventricular Systolic Pressure

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

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