scholarly journals PO-144 Intermittent Exercise Activates NRG1-SERCA2a Pathway to Improve Cardiac Function in Myocardial Infarction Rats

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Wenyan Bo ◽  
Dagang Li ◽  
Zhenjun Tian
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Protein Expression ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Intermittent Exercise ◽  
Critical Role ◽  
Interval Training ◽  
Sprague Dawley ◽  
Neuregulin 1

Objective  Intermittent exercise can improve cardiac function in rats with myocardial infarction. The Neuregulin-1(NRG1)/SERCA2a palys a critical role in maintain cardiac function. We want to investigate the effect of Neuregulin-1 (NRG1) on NRG1-SERCA2a signaling pathway activated by intermittent exercise and on improves cardiac function in rats with MI. Methods 32 male sprague-dawley rats were randomly divided into four groups (n=8): Sham-operated group (S), sedentary MI group (MI), MI with interval training group (ME), ME with inhibitor AG1478 group (MA). ME and MA model after the MI model was established by ligation of the left anterior descending coronary artery, and began training 1 week after MI surgery. The S model only by threading without ligation. Rats in ME and MA model taken one week adaptive training, then began 8-week interval training. MA model were injected with inhibitor AG1478, once every two days. The 24h after training, rats were anesthetized, the LVSP, LVEDP, ±dp/dt max were tested by carotid artery intubation which in order to evaluate cardiac function. The protein expression of NRG1, PI3K, Akt, eNOS, PKG, PLN, SERCA2a in myocardium were measured by Westernblotting, themRNA expression of serca2a were tested by RT-qPCR. Results Compared with S, the protein expression of NRG1, PKG, peNOS, pAkt, pPLN, pPI3K and SERCA2a decreased, serca2a mRNA expression decreased, LVSP and ±dp/dt max significantly decreased, LVEDP significantly increased; Compared with MI, the protein expression of NRG1, PKG, peNOS, pAkt, pPLN, pPI3K and SERCA2a increased, serca2a mRNA expression increased, LVSP and ±dp/dt max significantly increased, LVEDP decreased, and the effect of exercise were weaken by inhibitor AG1478. Correlation analysis showed that the myocardial pPLN and SERCA2a protein expression both were positively correlated with LVSP, ±dp/dtmax, and negatively correlated with LVEDP. Conclusions Intermittent exercise can increased myocardial NRG1 protein expression and activates NRG1-SERCA2a signaling pathway, improve myocardial infarction cardiac function.

scholarly journals Neuregulin-1 Promotes Myocardial Angiogenesis in Acute Myocardial Infarction Through Regulating PI3K-AKT-eNOS and VEGF/VEGFR2 Signal Pathways

2021 ◽  
Author(s):  
Xiao Ma ◽  
Chengqiang Wu ◽  
Lang Li ◽  
Zhiyu Zeng ◽  
Chun Gui
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Function ◽  
Function Analysis ◽  
Critical Role ◽  
Myocardial Damage ◽  
Capillary Density ◽  
Left Ventricular ◽  
Signal Pathways ◽  
Neuregulin 1

Abstract Background: Myocardial angiogenesis is central to the recovery of acute myocardial infarction (AMI). Neuregulin-1 (NRG-1) plays a critical role in cardiac function, although its role in myocardial angiogenesis is still unclear. The aim of this study was to investigate the effects of NRG-1 in myocardial angiogenesis in a rat model of AMI, and elucidate the underlying mechanisms. Methods: AMI was induced by a single ligation of left anterior descending coronary artery, followed by intravenous injection of recombinant human NRG-1 or normal saline for 8 consecutive days. The cardiac function indices were measured using the catheter MPA cardiac function analysis system. Histo-pathological changes were observed by HE. Microvessel density (MVD) was measured by CD31 and α-SMA immunostaining. The expression levels of other proteins were assessed by Western blotting. Results: NRG-1 improved cardiac function and alleviated myocardial damage induced by AMI. Compared to the sham-operated group, the capillary density and arteriole density increased after AMI (P<0.05), and were augmented by NRG-1 which also significantly increased the left ventricular function (P<0.05). Furthermore, Compared with sham group, PI3K-AKT-eNOS signaling was decreased significantly (P<0.05) whereas VEGF/ VEGFR2 signaling was significantly increased（P<0.05）in AMI group and both of therm were further upregulated by NRG-1 (P > 0.05).Conclusion: NRG-1 improved cardiac function and promoted myocardial angiogenesis post AMI by up-regulating VEGF and activating the PI3K-Akt-eNOS pathway.

Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler
Keyword(s):  
Myocardial Infarction ◽  
Drinking Water ◽  
Mineralocorticoid Receptor ◽  
Critical Role ◽  
Weight Ratio ◽  
Myocardial Necrosis ◽  
Receptor Activation ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

Electroacupuncture inhibits the corneal ROS/TXNIP/NLRP3 signaling pathway in a rat model of dry eye syndrome

2021 ◽  
pp. 096452842110392
Author(s):  
Yanting Yang ◽  
Dan Zhang ◽  
Lijie Wu ◽  
Ji Zhang ◽  
Danyan Wu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Dry Eye ◽  
Clinical Symptoms ◽  
Dry Eye Syndrome ◽  
Receptor Protein ◽  
Sprague Dawley ◽  
Corneal Injury ◽  
Caspase 1 ◽  
Des Model

Background: Electroacupuncture (EA) treatment has been found to ameliorate clinical symptoms in patients with dry eye, but its mechanisms are still not entirely clear. Objective: To study the regulation of EA on ocular surface function and the corneal reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/Nod-like receptor protein 3 (NLRP3) inflammatory signaling pathway in dry eye syndrome (DES) model rats. Methods: Male Sprague-Dawley (SD) rats were randomly divided into five groups: Normal, Model, Model + EA, Model + NAC (N-actetylcysteine) and Model + NS (normal saline). The DES model was developed by subcutaneous injection of scopolamine hydrobromide with exposure to an air draft in the latter four groups. After intervention, the Schirmer I test (SIT), tear film break-up time (BUT) and ROS content were measured, the histopathological changes of corneal tissues were observed, and the mRNA and protein expression levels of TXNIP, NLRP3, apoptosis-associated Speck-like protein containing CARD (ASC), caspase-1, interleukin (IL)-1β and IL-18 were detected. Results: Compared with the Model group, the SIT and BUT increased significantly in the Model + EA group after intervention (p < 0.05), and the corneal injury was improved. Corneal ROS content declined in both Model + EA and Model + NAC groups (p < 0.05), and mRNA expression of TXNIP, NLRP3, ASC and caspase-1 also decreased (p < 0.01). Corneal protein expression of TXNIP, NLRP3, IL-1β and IL-18 decreased significantly in the Model + EA group (p < 0.01). Conclusion: Inhibiting the ROS/TXNIP/NLRP3 signaling pathway may be the mechanism underlying the role of EA in improving corneal injury in DES model rats.

scholarly journals Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

2022 ◽  
Vol 8 ◽  
Author(s):  
Zhi Li ◽  
Miao Nie ◽  
Liming Yu ◽  
Dengshun Tao ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Macrophage Polarization ◽  
Notch Signaling Pathway ◽  
Inflammatory Factors ◽  
M2 Macrophage ◽  
M2 Polarization

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

Abstract 352: Myocardial Neuregulin-1/ErbB Signaling Is Impaired in the Setting of Post--Myocardial Infarction Heart Failure Complicated by Type 1 Diabetes Mellitus

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Oghenerukevwe Odiete ◽  
Kathleen E Dennis ◽  
Douglas B Sawyer ◽  
Michael F Hill
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 1 Diabetes ◽  
Protein Expression ◽  
Type 1 Diabetes Mellitus ◽  
Neuregulin 1 ◽  
Erbb Signaling ◽  
Type 1 Dm

Background: Type 1 diabetes mellitus (DM) patients surviving myocardial infarction (MI) are at heightened risk for the subsequent development of heart failure (HF). Despite the worse outcomes, investigations into the pathophysiological mechanisms that contribute to the increased frequency of HF after MI in the type 1 DM heart remain scarce. Neuregulin-1 (NRG-1), along with the ErbB family of receptor tyrosine kinases through which NRG-1 ligands signal, have been shown to be intimately involved in mediating cardiac recovery after MI. However, the impact of type 1 DM on this signaling system post-MI remains to be elucidated. Therefore, in the present study, we examined myocardial NRG-1/ErbB signaling during post-MI HF in the presence of type 1 DM. Methods: Type 1 DM was induced in male Sprague-Dawley rats via a single intraperitoneal injection of streptozotocin (STZ) (65 mg/kg). Two weeks after induction of type 1 DM, MI was produced in DM and non-DM rats by ligation of the left anterior descending (LAD) coronary artery. Residual left ventricular (LV) function was assessed by echocardiography at 4 weeks post-MI. Following echocardiographic assessment, NRG-1, ErbB2, and ErbB4 protein expression was assessed in the remote, surviving LV myocardium of DM and non-DM rats using Western blot techniques. Results: LV Fractional Shortening (FS) and LV Ejection Fraction (EF) were significantly lower in the DM + MI group compared to the MI group ([LVFS: DM + MI, 17.9 ± 0.7 (n=6) vs. MI, 25.2 ± 2.2 (n=6), p <0.05; LVEF: DM + MI, 35.5 ± 1.4 (n=6) vs. MI, 47.5 ± 3.5 (n=6), p <0.05]), indicating an increased functional severity of HF in the diabetic post-MI group. The weight of myocardial scar caused by the infarction was not significantly different between the MI groups ([DM + MI, 0.19 ± 0.02 g (n=4) vs. MI, 0.20 ± 0.03 g (n=4), p =0.70]). ErbB2, ErbB4, and NRG-1 protein expression levels were all significantly lower in the DM + MI group compared to the MI group. Conclusions: These findings demonstrate that type 1 DM impairs myocardial NRG-1/ErbB signaling in response to MI, which may contribute to the accelerated progression of subsequent HF. Augmentation of NRG-1 or its downstream signaling pathways may represent a novel therapeutic strategy for ameliorating post-MI HF in the setting of type 1 DM.

Abstract 388: ICV Angiotensin-(1-7) Improves Cardiac Function and Attenuates Remodeling In (mren2)27 Transgenic Hypertensive Rats

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Lucas M Kangussu ◽  
Marcos B Melo ◽  
Priscila S Guimarães ◽  
Ana P Nadu ◽  
Michael Bader ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Natriuretic Peptide ◽  
Critical Role ◽  
Renin Angiotensin System ◽  
Vagal Activity ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
The Central Nervous System ◽  
Tgf Β1

Overactivity of the renin-angiotensin system (RAS), through Ang II/AT1 axis, plays a critical role in the pathogenesis of cardiovascular diseases. On the other hand, Ang-(1-7)/Mas axis is recognized to attenuate the deleterious effects of the RAS at different sites including the central nervous system. In the present study, Sprague Dawley (SD) and transgenic hypertensive rats (mRen2)27, instrumented with telemetry probes for arterial pressure (AP) measurements, were subjected to 14 days of lateral ventricle (ICV) infusion of Ang-(1-7) (200 ng/h) alone, Ang-(1-7) (200 ng/h) in association with a Mas receptor antagonist (A779, 1 μg/h) or saline (0.5 ml/hour) through osmotic mini-pumps. Ang-(1-7) ICV attenuated hypertension of (mRen2)27 rats (144±8 mmHg vs 174±3 mmHg, before. The AP lowering effect of ICV Ang-(1-7) was completely blocked by A779 (174±12 mmHg). Cardiac hypertrophy and dysfunction, evaluated by echocardiography, of (mRen2)27 rats were attenuated in Ang-(1-7) infused rats. The increased levels of atrial natriuretic peptide, brain natriuretic peptide, collagen I, fibronectin and TGF-β1 in the heart of (mRen2)27 rats were significantly reduced by Ang-(1-7) infusion and partially reversed by the concomitant infusion of A-779. Further, cardiac effects induced by ICV Ang-(1-7) were accompanied by an attenuation of the increased ratio sympathetic/ vagal activity to the heart of (mRen2)27. The data of the present study indicate that short-term central infusion of Ang-(1-7) produces Mas-mediate improvement in cardiac function and attenuates cardiac remodeling in (mRen2)27 hypertensive rats, probably through an improvement of the autonomic balance to the heart. Support: CAPES and FAPEMIG/CNPq through INCT-NanoBioFar and PRONEX.

scholarly journals Cardioprotective Effect of Danhong Injection against Myocardial Infarction in Rats Is Critically Contributed by MicroRNAs

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jingrui Chen ◽  
Jing wei ◽  
John Orgah ◽  
Yan Zhu ◽  
Jingyu Ni ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Nuclear Translocation ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Danhong Injection ◽  
Sprague Dawley Rats ◽  
Masson Staining

Background. Danhong injection (DHI) has been mainly used for the treatment of myocardial infarction, atherosclerosis, and coronary heart disease in clinical practice. Our previous studies have shown that DHI improves ventricular remodeling and preserves cardiac function in rats with myocardial infarction (MI). In this study, we focused on the potential mechanism of DHI in protecting cardiac function in MI rats. Methods. Sprague-Dawley rats were subjected to ligation of the left anterior descending coronary artery (LAD) to prepare a myocardial infarction (MI) model. After 14 day DHI intervention, cardiac function was measured by echocardiography and myocardial fibrosis was assessed by Masson staining. Differentiated miRNAs were screened using rat immunopathology miScript miRNA PCR arrays, and their results were verified by RT-PCR, immunofluorescence, and immunoblotting. Results. DHI treatment significantly reduced infarct size and improved cardiac function and hemodynamics in MI rats by echocardiography and morphology. miRNA PCR array results showed that DHI reversed 25 miRNAs known to be associated with inflammation and apoptosis. Moreover, the expression of inflammatory factors TNF-α, IL-1β, and IL-6 was significantly reduced in the treated DHI group. Mechanistically, DHI downregulated the inflammatory transcription factor NF-κB (as reflected by inhibition of NF-κB p65 nuclear translocation and phosphorylation of the IκBα). Conclusions. DHI is effective in mitigating inflammation associated with MI by preventing NF-κB nuclear translocation and regulating miRNAs, thereby improving cardiac function in myocardial infarction rats.

Effects of carbon nanotube-mediated Caspase3 gene silencing on cardiomyocyte apoptosis and cardiac function during early acute myocardial infarction

Nanoscale ◽  
2020 ◽  
Vol 12 (42) ◽  
pp. 21599-21604
Author(s):  
Yi Li ◽  
Hong Yu ◽  
Liang Zhao ◽  
Yuting Zhu ◽  
Rui Bai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Gene Silencing ◽  
Ventricular Remodeling ◽  
Myocardial Cell ◽  
Coronary Artery Ligation ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Sd Rats

Caspase3 gene silencing based on the gene transfer carrier F-CNT-siCas3 had obvious protective effects on myocardial cell apoptosis, ventricular remodeling, and cardiac function in Sprague-Dawley (SD) rats after coronary artery ligation.

scholarly journals GPR30 Activation by 17β-Estradiol Promotes p62 Phosphorylation and Increases Estrogen Receptor α Protein Expression by Inducing Its Release from a Complex Formed with KEAP1

2021 ◽  
Vol 11 (9) ◽  
pp. 906
Author(s):  
Chia-Lung Tsai ◽  
Chiao-Yun Lin ◽  
Angel Chao ◽  
Yun-Shien Lee ◽  
Ren-Chin Wu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Critical Role ◽  
Adaptor Protein ◽  
Estrogen Receptor Α ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
17Β Estradiol ◽  
Esr1 Expression

Estrogens can elicit rapid cellular responses via the G-protein-coupled receptor 30 (GPR30), followed by estrogen receptor α (ERα/ESR1)-mediated genomic effects. Here, we investigated whether rapid estrogen signaling via GRP30 may affect ESR1 expression, and we examined the underlying molecular mechanisms. The exposure of human endometrial cancer cells to 17β-estradiol promoted p62 phosphorylation and increased ESR1 protein expression. However, both a GPR30 antagonist and GPR30 silencing abrogated this phenomenon. GPR30 activation by 17β-estradiol elicited the SRC/EGFR/PI3K/Akt/mTOR signaling pathway. Intriguingly, unphosphorylated p62 and ESR1 were found to form an intracellular complex with the substrate adaptor protein KEAP1. Upon phosphorylation, p62 promoted ESR1 release from the complex, to increase its protein expression. Given the critical role played by p62 in autophagy, we also examined how this process affected ESR1 expression. The activation of autophagy by everolimus decreased ESR1 by promoting p62 degradation, whereas autophagy inhibition with chloroquine increased ESR1 expression. The treatment of female C57BL/6 mice with the autophagy inhibitor hydroxychloroquine—which promotes p62 expression—increased both phosphorylated p62 and ESR1 expression in uterine epithelial cells. Collectively, our results indicate that 17β-estradiol-mediated GPR30 activation elicits the SRC/EGFR/PI3K/Akt/mTOR signaling pathway and promotes p62 phosphorylation. In turn, phosphorylated p62 increased ESR1 expression by inducing its release from complexes that included KEAP1. Our findings may lead to novel pharmacological strategies aimed at decreasing ESR1 expression in estrogen-sensitive cells.

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