P3486Experimental model for heart failure in rats: apelin-13/apj and bnp-45 gene expression analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H R Helmi ◽  
A P Sunjaya ◽  
D Limanan ◽  
A R Prijanti ◽  
S W A Jusman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Rat Model ◽  
Control Group ◽  
P Value ◽  
Sprague Dawley ◽  
Hypoxia Exposure ◽  
Systemic Hypoxia

Abstract Background Apelin, an adipokine peptide and its receptor has recently emerged as a key signaling pathway in maintaining cardiac performance at chronic pressure loads. Apelin has been linked to ventricular dysfunction and therefore maybe of pathophysiologic relevance as a candidate biomarker in HF patients. Purpose This study aims to investigate Apelin-13 gene expression and level, and Apelin receptor (APJ) level in a rat model of heart failure induced by chronic systemic hypoxia and their correlation to BNP-45 gene expression and level, the current gold standard biomarker for heart failure, and to cardiac histopathologic changes. The effect of chronic systemic hypoxia on cardiac hypertrophy, remodeling and heart failure parameters is also of interest. Methods Twenty-eight male Sprague-Dawley rats (8–12 weeks of age) were placed in special hypoxic chambers divided into 7 groups – a control group provided with normoxia (atmospheric O2 levels) and 6 exposure groups exposed to hypoxia (8% O2) for 6 hours, 1, 3, 5, 7 and 14 days respectively prior to measurement. Changes in the expression of Apelin and BNP-45 were measured using quantitative real-time PCR, whereas changes in Apelin-13, APJ and BNP-45 levels were measured using ELISA. Histopathology staining using Hematoxylin and Eosin was performed on cardiac tissues post-termination. Results Compared to control, BNP-45 mRNA expression in the hypoxic heart was only significantly different in day 14, whereas, Apelin mRNA expression had showed significantly higher values starting from day 7 onward. This is in line with the evidence of cardiac hypertrophy based on histopathologic examination present from day 7 onwards. BNP-45 and Apelin-13 levels were significantly higher compared to control from day 5 onwards with a peak on day 7. Although significantly higher than control, Apelin-13 and BNP-45 level decreases in day 14 as compared to day 7. Mean APJ levels showed a similar profile with Apelin-13 and BNP-45 levels with a peak in day 7 (4.619 ng/mL). The cardiac Apelin-13 level shows strong significant correlation with BNP-45 levels (r 0.823, p-value 0.0001). There was also a strong significant correlation between APJ receptor levels with Apelin-13 (r 0.9029, p-value 0.001) and BNP-45 (r 0.9062, p-value 0.0009) levels. Apelin-13, APJ and BNP-45 levels also showed strong significant positive correlation to the duration of hypoxia exposure. Conclusion Chronic (≥5 days) and not acute systemic hypoxia in an experimental rat model leads to increase in Apelin-13, APJ and BNP-45 levels. Apelin-13 and BNP-45 were found to significantly increase from 5 days onwards. Apelin mRNA expression was found to show significant increase earlier compared to BNP-45 mRNA expression. Hence, Apelin may serve as a new candidate biomarker for detection of HF due to oxidative stress compared to BNP-45. Exposure to chronic systemic hypoxia can serve as an easily replicable rat model for heart failure. Acknowledgement/Funding Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia

Upregulation of corin gene expression in hypertrophic cardiomyocytes and failing myocardium

2004 ◽  
Vol 287 (4) ◽  
pp. H1625-H1631 ◽  
Author(s):  
Katherine L. Tran ◽  
Xiangru Lu ◽  
Ming Lei ◽  
Qingping Feng ◽  
Qingyu Wu
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Mrna Expression ◽  
Rat Model ◽  
Left Ventricular ◽  
Biologically Active ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Neonatal Cardiomyocytes

High levels of plasma atrial natriuretic peptides (ANP) are associated with pathological conditions such as congestive heart failure (CHF). Recently, we have identified a cardiac serine protease, corin, that is the pro-ANP convertase. In this study, we examined the regulation of corin gene expression in cultured hypertrophic cardiomyocytes and in the left ventricular (LV) myocardium of a rat model of heart failure. Quantitative RT-PCR analysis showed that both corin and ANP mRNA levels were significantly increased in phenylephrine (PE)-stimulated rat neonatal cardiomyocytes in culture. The increase in corin mRNA correlated closely with the increase in cell size and ANP mRNA expression in the PE-treated cells ( r = 0.95, P < 0.01; r = 0.92, P < 0.01, respectively). The PE-treated cardiomyocytes had an increased activity in converting recombinant human pro-ANP to biologically active ANP, as determined by a pro-ANP processing assay and a cell-based cGMP assay. In a rat model of heart failure induced by ligation of the left coronary artery, corin mRNA expression in the noninfarcted LV myocardium was significantly higher than that of control heart tissues from sham-operated animals, when examined by Northern blot analysis and RT-PCR at 8 wk. These results indicate that the corin gene is upregulated in hypertrophic cardiomyocytes and failing myocardium. Increased corin expression may contribute to elevation of ANP in the setting of cardiac hypertrophy and heart failure.

scholarly journals EVALUATION OF CHONDROPROTECTIVE EFFICACY OF TRIAMCINOLONE IN OSTEOARTHRITIS INDUCED RAT MODEL

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Noaman Ishaq ◽  
Quratulain Mehdi ◽  
Novera Sohail Bajwa ◽  
Shabana Ali ◽  
Bushra Shaheen ◽  
...  
Keyword(s):  
Treatment Group ◽  
Rat Model ◽  
Cruciate Ligament ◽  
Gait Pattern ◽  
Control Group ◽  
P Value ◽  
Surgical Removal ◽  
Sprague Dawley ◽  
Medical College ◽  
Group I

ABSTRACT BACKGROUND AND OBJECTIVE: Osteoarthritis is one of the most common joint diseases afflicting human, characterized by progressive degeneration of articular cartilage in which chondrocytes fails to adequately repair. Objective of this study is to evaluate the chondroprotection offered by triamcinolone in osteoarthritis induced rat model METHODOLOGY: This Laboratory based experimental study was conducted in Department of Pharmacology, Army Medical College, Rawalpindi, in collaboration with National Institute of health, Islamabad from April-June2019. Osteoarthritis was induced by surgical removal of medial meniscus and anterior cruciate ligament resection in right knee joint of Sixteen (16) anesthetized rats of Sprague Dawley breed. They were divided in two (02) groups with eight (08) rats in each group. Group I was disease control in which 0.2 ml Intra articular saline was administered for three weeks. While group II was treatment group that was treated by 70 µl intra articular triamcinolone once weekly for three weeks. After that gait pattern of rats was scored. Animals were euthanized with over dosage of inhaled chloroform and sample of proximal tibia was taken for histopathological analysis.RESULTS: Mean gait score of control group and treatment group was 3.25±.707 and 2.25±.463 with a p value of .028 that is statistically significant. While mean histopathological modified Mankin score of control and treatment group was 11.5±1.195 and 8.5±1.195 respectively with a significant P-value of <0.01. CONCLUSION: Intra articular administration of triamcinolone in Osteoarthritis induced rats resulted in improvement in gait pattern and histopathology. Keywords: Chondroprotective efficacy, Osteoarthritis, Triamcinolone.

scholarly journals CYTOGLOBIN EXPRESSION IN RAT KIDNEY DURING EXPOSURE TO SYSTEMIC CHRONIC HYPOXIA

2020 ◽  
Vol 3 (1) ◽  
pp. 30-36
Author(s):  
Ika Superti Daruningrum ◽  
Sri Widia A Jusman ◽  
Ninik Mudjihartin ◽  
Ani Retno Prijanti ◽  
Mohamad Sadikin
Keyword(s):  
Oxygen Supply ◽  
Rat Kidney ◽  
Control Group ◽  
Sprague Dawley ◽  
Physiological Conditions ◽  
Hypoxia Exposure ◽  
Hypoxic Conditions ◽  
Sprague Dawley Rats ◽  
Systemic Hypoxia ◽  
Adaptation Response

Background:  The kidneys in physiological conditions are always in a state of relative hypoxia. Cytoglobin (Cygb) is the newest globin protein found of the globin family. One of the functions of Cygb is in oxygen supply. Cygb expression is found to increase in hypoxic conditions, which are thought to be an adaptation response to hypoxia.  Objective: This study aimed to analyze the expression of Cygb in rat kidneys which were exposed to chronic systemic hypoxia.Methods: Twenty five male Sprague-Dawley rats, weighing 150-200 g were used in this experiment. Rats were divided into 5 groups: The control group was exposed to normoxia; the hypoxia groups (10% oxygen / 90% nitrogen) for 1 day; 3 days; 7 days and 14 days. After treatment, rats were sacrificed and their kidneys were taken. Cygb mRNA expression was measured by qRT-PCR, while Cygb protein expression was measured by the ELISA method.Results: The expressions of Cygb mRNA and protein were found to be highest on day 3 of hypoxia and was correlated very strongly and significantly (r2 = 0.96; p <0.05).Conclusion: The highest expression of Cygb on day 3 of chronic systemic hypoxia exposure is suggested as an attempt to restore oxygen supply to the kidneys.

scholarly journals Elevated Levels of Apelin-36 in Heart Failure Due to Chronic Systemic Hypoxia

2018 ◽  
Vol 28 (03) ◽  
pp. 194-199
Author(s):  
Frans Ferdinal ◽  
David Limanan ◽  
Retno Dwi Rini ◽  
Rio Alexsandro ◽  
Rizal Helmi
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Structural Damage ◽  
Molecular Mechanisms ◽  
Ventricular Remodeling ◽  
Biological Effects ◽  
Orphan Receptor ◽  
Control Group ◽  
Sprague Dawley ◽  
Systemic Hypoxia

AbstractApelin is a novel adipokine identified as an endogenous ligand of the specific orphan receptor APJ. Among the various isoforms of apelin, an increase in the apelin-36 plasma level has been associated with oxidative stress, and this isoform has various biological effects, such as positive inotropic, vasodilatory, and antiatherosclerotic effects. Therefore, apelin-36 may be used as a biomarker of heart failure (HF). Advances in the understanding of the molecular mechanisms underlying HF cannot be achieved without the use of animal models. However, it is unclear whether chronic systemic hypoxia can cause HF in rats. The present study aimed to determine whether chronic systemic hypoxia can cause HF in rats and whether apelin-36 can be used as a biomarker of HF. The study included Sprague–Dawley rats. The rats were randomly divided into seven groups (n = 4). One of the groups was a control group, and the six other groups were exposed to hypoxia (8% O2) for different durations (6 hours, 1 day, 3 days, 5 days, 7 days, and 14 days). The exposure groups showed ventricular hypertrophy accompanied by myocardial structural damage, which indicated ventricular remodeling. In addition, the exposure groups showed elevated apelin-36 plasma levels and signs of oxidative stress. Moreover, gel electrophoresis of heart tissue showed five bands that corresponded to apelin isotypes, including apelin-36. In an experimental rat HF model with chronic systemic hypoxia, apelin-36 was elevated along with oxidative stress. Apelin-36 along with oxidative stress may serve as a biomarker of HF in this model.

scholarly journals Gene expression and enzyme activities of carbonic anhydrase and glutaminase in rat kidneys induced by chronic systemic hypoxia

2015 ◽  
Vol 24 (3) ◽  
pp. 139-45
Author(s):  
Andi N.K. Syarifin ◽  
Sri W.A. Jusman ◽  
Mohamad Sadikin
Keyword(s):  
Gene Expression ◽  
Carbonic Anhydrase ◽  
Enzyme Activities ◽  
Specific Activity ◽  
Kidney Tissue ◽  
Control Group ◽  
Strong Positive Correlation ◽  
Sprague Dawley ◽  
Acid Base Balance ◽  
Systemic Hypoxia

Background: Hypoxia can cause acidosis. Kidney plays an essential role in maintaining acid-base balance, which involves the activities of carbonic anhydrase (CA) and glutaminase (GLS). This study is aimed to determine the expression and activities of the CA9 and GLS1 enzymes in relation to hypoxia inducible factor-1α (HIF-1α), a transcription factor protein which is a marker of hypoxia.Methods: This study was an in vivo experimental study with coupled paralel design. used 25 male Sprague-Dawley rats weighing 150-200 g. Rats were divided into 5 groups: the control group (normoxic condition) and 4 treatment groups. The latter were kept in a hypoxic chamber (10% O2: 90% N2) for 1, 3, 5 and 7 days. All rats were euthanized after treatment, kidneys excised, tissues homogenized and investigated for gene expression of CA9, GLS1 and HIF-1α. On protein level, total enzymatic activities of CA and GLS and protein of HIF-1α were also investigated. Data were analyzed statistically using ANOVA for significance, and as its alternative, used Mann-Whitney and Kruskal-Wallis test.Results: Results showed that HIF-1α mRNA increased during hypoxia, but not HIF-1α protein. It seemed that acidosis occurs in kidney tissue, indicated by increased CA9 and GLS1 mRNA expression and specific activity of total CA and GLS1. Expression of CA9 and GLS1 mRNA both showed strong positive correlation with HIF-1α mRNA, but not with HIF-1α protein.Conclusion: It is suggested that during chronic systemic hypoxia, gene expression of CA9 and GLS1 and their enzyme activities were increased as a response to acidosis and related with the expression of HIF-1α mRNA.

scholarly journals Effects of Vitrification on the Blastocyst Gene Expression Profile in a Porcine Model

2021 ◽  
Vol 22 (3) ◽  
pp. 1222
Author(s):  
Cristina Cuello ◽  
Cristina A. Martinez ◽  
Josep M. Cambra ◽  
Inmaculada Parrilla ◽  
Heriberto Rodriguez-Martinez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Survival Rates ◽  
Control Group ◽  
P Value ◽  
Transcriptome Profile ◽  
Embryo Viability ◽  
The Impact

This study was designed to investigate the impact of vitrification on the transcriptome profile of blastocysts using a porcine (Sus scrofa) model and a microarray approach. Blastocysts were collected from weaned sows (n = 13). A total of 60 blastocysts were vitrified (treatment group). After warming, vitrified embryos were cultured in vitro for 24 h. Non-vitrified blastocysts (n = 40) were used as controls. After the in vitro culture period, the embryo viability was morphologically assessed. A total of 30 viable embryos per group (three pools of 10 from 4 different donors each) were subjected to gene expression analysis. A fold change cut-off of ±1.5 and a restrictive threshold at p-value < 0.05 were used to distinguish differentially expressed genes (DEGs). The survival rates of vitrified/warmed blastocysts were similar to those of the control (nearly 100%, n.s.). A total of 205 (112 upregulated and 93 downregulated) were identified in the vitrified blastocysts compared to the control group. The vitrification/warming impact was moderate, and it was mainly related to the pathways of cell cycle, cellular senescence, gap junction, and signaling for TFGβ, p53, Fox, and MAPK. In conclusion, vitrification modified the transcriptome of in vivo-derived porcine blastocysts, resulting in minor gene expression changes.

Use of genechips to analyse gene expression patterns in a rat model of ischemic heart failure

2002 ◽  
Vol 34 (6) ◽  
pp. A22
Author(s):  
Barbara Fellner ◽  
Karola Trescher ◽  
Severin Semsroth ◽  
Karin Hoffmann-Sommergruber ◽  
Wolfgang Schmidt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Rat Model ◽  
Expression Patterns ◽  
Ischemic Heart ◽  
Gene Expression Patterns ◽  
Ischemic Heart Failure

scholarly journals A Subpressor Dose of Angiotensin II Elevates Blood Pressure in a Normotensive Rat Model by Oxidative Stress

2015 ◽  
pp. 153-159 ◽  
Author(s):  
M. M. GOVENDER ◽  
A. NADAR
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Mrna Expression ◽  
Rat Model ◽  
Wistar Rat ◽  
Control Group ◽  
Sod Activity ◽  
Male Wistar Rats ◽  
Experimental Group

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2− production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.

scholarly journals PIJAT KAKI EFEKTIF MENURUNKAN FOOT EDEMA PADA PENDERITA CONGESTIVE HEART FAILURE (CHF)

2019 ◽  
Vol 2 (1) ◽  
pp. 14
Author(s):  
Kasron Kasron
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Wilcoxon Test ◽  
Control Group ◽  
P Value ◽  
Probability Sampling ◽  
Post Test ◽  
Quasi Experiment

Oedema kaki merupakan salah satu gejala pada pasien CHF. Oedema kaki dapat menyebabkan penurunan kualitas hidup, ketidaknyamanan, perubahan postur tubuh, menurunkan mobilitas dan meningkatkan resiko jatuh, gangguan sensasi di kaki dan menyebabkan perlukaan di kulit. Tujuan penelitian untuk mengetahui pengaruh pijat kaki terhadap penurunan oedema kaki pada pasien CHF. Metode penelitian menggunakan quasi-experiment dengan pendekatan pre-post test without control group. Responden penelitian adalah pasien CHF yang mengalami oedema kaki, pemilihan responden menggunakan non-probability sampling dengan metode accidental sampling. Responden diukur lingkar oedema pada lingkar angkle, instep dan MP-Joint menggunakan metline pada sebelum intervensi, hari pertama, kedua dan ketiga. Analisis statistik menggunakan wilcoxon test. Sejumlah 13 responden memenuhi kriteria penelitian. Pada kaki kanan lingkar angkle pre: 27,7±1,8, post 1: 27,6±1,8, post 2 27,5±1,7, post 3: 27,2±1,7, lingkar instep pre: 27,6±1,7, post 1: 27,6±1,8, post 2: 27,2±1,7, post 3: 26,9±1,7, lingkar MP-joint pre: 27,0±1,6, post 1: 27,0±1,6, post 1: 27,0±1,6, post 2: 26,7±1,7, post 3: 26,3±1,7. Kaki kiri lingkar angkle pre: 27,6±1,8, post 1: 27,6±1,8, post 2: 27,3±1,8, post 3: 27,0±1,8, lingkar instep pre: 27,6±1,7, post 1: 27,5±1,7, post 2: 27,2±1,7, post 3: 26,8±1,7, lingkar MP-joint pre: 27,0±1,6, post 1: 26,9±1,8, post 2: 26,5±1,8, post 3: 26,2±1,8. Hasil analisis menunjukan bahwa terdapat perbedaan yang bermakna lingkar oedema pada kaki kanan setelah hari kedua dan ketiga dengan p-value <0,001. Kesimpulan penelitian adalah terdapat perbedaan lingkar oedema angkle, instep, dan MP-joint pada hari kedua dan ketiga setelah pemijatan kaki pada pasien CHF yang mengalami oedema kaki. Perlu penelitian lanjutan untuk penatalaksanaan oedema kaki pada pasien CHF yang mengalami oedema kaki.

Discovery of Serum Proteomic Biomarkers for Prediction of Response to Moxibustion Treatment in Rats with Collagen-Induced Arthritis: An Exploratory Analysis

2016 ◽  
Vol 34 (3) ◽  
pp. 184-193 ◽  
Author(s):  
Xiao Xu ◽  
Miao-Miao Wang ◽  
Zhi-ling Sun ◽  
Dan-ping Zhou ◽  
Ling Wang ◽  
...  
Keyword(s):  
Rat Model ◽  
Multiple Testing ◽  
Day Treatment ◽  
Expression Patterns ◽  
Control Group ◽  
Sprague Dawley ◽  
Collagen Induced Arthritis ◽  
Serum Samples ◽  
Beneficial Effects ◽  
Bovine Collagen

Objective To examine the possible impact of moxibustion on the serum proteome of the collagen-induced arthritis (CIA) rat model. Materials and Methods Thirty-six male Sprague-Dawley rats were included in this experiment. The CIA animal model was prepared by injection of type II bovine collagen in Freund's adjuvant on the first and seventh day. The 36 rats were randomly divided into two groups: the untreated CIA group (control), and the CIA plus treatment with moxibustion (CIA+moxi) group. Moxibustion was administered daily at ST36 and BL23 for 7, 14 or 21 days (n=12 rats each). Arthritis score was used to assess the severity of arthritis. At the end of each 7 day treatment, blood samples from the control group and the CIA+moxi group were collected. After removal of high abundance proteins from serum samples, two-dimensional gel combined with matrix-assisted laser desorption ionisation time-of-flight MS/MS (MALDI-TOF-MS/MS) techniques were performed to examine serum protein expression patterns of the CIA rat model with and without moxibustion treatment. In addition, the relevant proteins were further analysed with the use of bioinformatics analysis. Results Moxibustion significantly decreased arthritis severity in the rats in the CIA+moxi group, when compared with the rats in the CIA group 35 days after the first immunisation (p=0.001). Seventeen protein spots which changed >1.33 or <0.77 at p<0.05 using Bonferonni correction for multiple testing were found to be common to all three comparisons, and these proteins were used for classification of functions using the Gene Ontology method. Consequently, with the use of the Ingenuity Pathway Analysis, the top canonical pathways and a predicted proteomic network related to the moxibustion effect of CIA were established. Conclusions Using the proteomics technique, we have identified novel candidate proteins that may be involved in the mechanisms of action underlying the beneficial effects of moxibustion in rats with CIA. Our findings suggest that immune responses and metabolic processes may be involved in mediating the effects of moxibustion. Moreover, periodxiredoxin I (PRDX1) and inositol 1,4,5-triphosphate receptor (IP3R) may be potential targets.

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