scholarly journals Cardiac Connexin-43 and PKC Signaling in Rats With Altered Thyroid Status Without and With Omega-3 Fatty Acids Intake

2016 ◽  
pp. S77-S90 ◽  
Author(s):  
B. SZEIFFOVÁ BAČOVÁ ◽  
T. EGAN BEŇOVÁ ◽  
C. VICZENCZOVÁ ◽  
T. SOUKUP ◽  
H. RAUCHOVÁ ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Thyroid Hormones ◽  
Connexin 43 ◽  
Heart Function ◽  
Electrical Coupling ◽  
Omega 3 ◽  
Thyroid Status ◽  
Pkc Epsilon ◽  
Coupling Protein ◽  
Altered Thyroid

Thyroid hormones are powerful modulators of heart function and susceptibility to arrhythmias via both genomic and non-genomic actions. We aimed to explore expression of electrical coupling protein connexin-43 (Cx43) in the heart of rats with altered thyroid status and impact of omega-3 polyunsaturated fatty acids (omega-3) supplementation. Adult male Lewis rats were divided into following six groups: euthyroid controls, hyperthyroid (treated with T3) and hypothyroid (treated with methimazol) with or without six-weeks lasting supplementation with omega-3 (20 mg/100 g/day). Left and right ventricles, septum and atria were used for immunoblotting of Cx43 and protein kinase C (PKC). Total expression of Cx43 and its phosphorylated forms were significantly increased in all heart regions of hypothyroid rats compared to euthyroid controls. In contrast, the total levels of Cx43 and its functional phosphorylated forms were decreased in atria and left ventricle of hyperthyroid rats. In parallel, the expression of PKC epsilon that phosphorylates Cx43, at serine 368, was increased in hypothyroid but decreased in hyperthyroid rat hearts. Omega-3 intake did not significantly affect either Cx43 or PKC epsilon alterations. In conclusion, there is an inverse relationship between expression of cardiac Cx43 and the levels of circulating thyroid hormones. It appears that increased propensity of hyperthyroid while decreased of hypothyroid individuals to malignant arrhythmias may be in part attributed to the changes in myocardial Cx43.

scholarly journals Cardiac Cx43 and ECM Responses to Altered Thyroid Status Are Blunted in Spontaneously Hypertensive versus Normotensive Rats

2019 ◽  
Vol 20 (15) ◽  
pp. 3758 ◽  
Author(s):  
Matus Sykora ◽  
Barbara Szeiffova Bacova ◽  
Tamara Egan Benova ◽  
Miroslav Barancik ◽  
Jitka Zurmanova ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Connexin 43 ◽  
Transforming Growth Factor ◽  
Heart Function ◽  
Omega 3 ◽  
Thyroid Status ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Altered Thyroid

Heart function and its susceptibility to arrhythmias are modulated by thyroid hormones (THs) but the responsiveness of hypertensive individuals to thyroid dysfunction is elusive. We aimed to explore the effect of altered thyroid status on crucial factors affecting synchronized heart function, i.e., connexin-43 (Cx43) and extracellular matrix proteins (ECM), in spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto rats (WKRs). Basal levels of circulating THs were similar in both strains. Hyperthyroid state (HT) was induced by injection of T3 (0.15 mg/kg b.w. for eight weeks) and hypothyroid state (HY) by the administration of methimazol (0.05% for eight weeks). The possible benefit of omega-3 polyunsaturated fatty acids (Omacor, 200 mg/kg for eight weeks) intake was examined as well. Reduced levels of Cx43 in SHRs were unaffected by alterations in THs, unlike WKRs, in which levels of Cx43 and its phosphorylated form at serine368 were decreased in the HT state and increased in the HY state. This specific Cx43 phosphorylation, attributed to enhanced protein kinase C-epsilon signaling, was also increased in HY SHRs. Altered thyroid status did not show significant differences in markers of ECM or collagen deposition in SHRs. WKRs exhibited a decrease in levels of profibrotic transforming growth factor β1 and SMAD2/3 in HT and an increase in HY, along with enhanced interstitial collagen. Short-term intake of omega-3 polyunsaturated fatty acids did not affect any targeted proteins significantly. Key findings suggest that myocardial Cx43 and ECM responses to altered thyroid status are blunted in SHRs compared to WKRs. However, enhanced phosphorylation of Cx43 at serine368 in hypothyroid SHRs might be associated with preservation of intercellular coupling and alleviation of the propensity of the heart to malignant arrhythmias.

scholarly journals Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 546 ◽  
Author(s):  
Barbara Szeiffova Bacova ◽  
Csilla Viczenczova ◽  
Katarina Andelova ◽  
Matus Sykora ◽  
Kiranj Chaudagar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Connexin 43 ◽  
Electrical Coupling ◽  
Threshold Current ◽  
Prolonged Treatment ◽  
Diffuse Fibrosis ◽  
Omega 3 ◽  
Hypertensive Rats ◽  
Protein Levels ◽  
Coupling Protein

Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced β-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-β1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKCε, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats.

Altered thyroid status affects myocardial expression of connexin-43 and susceptibility of rat heart to malignant arrhythmias that can be partially normalized by red palm oil intake

2016 ◽  
Vol 147 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Barbara Szeiffová Bačová ◽  
Csilla Vinczenzová ◽  
Jitka Žurmanová ◽  
Dita Kašparová ◽  
Vladimír Knezl ◽  
...  
Keyword(s):  
Palm Oil ◽  
Rat Heart ◽  
Connexin 43 ◽  
Thyroid Status ◽  
Red Palm Oil ◽  
Altered Thyroid ◽  
Malignant Arrhythmias

Myocardial NOS activity and connexin-43 expression in untreated and omega-3 fatty acids-treated spontaneously hypertensive and hereditary hypertriglyceridemic rats

2010 ◽  
Vol 347 (1-2) ◽  
pp. 163-173 ◽  
Author(s):  
Jana Radosinska ◽  
Barbara Bacova ◽  
Iveta Bernatova ◽  
Jana Navarova ◽  
Anna Zhukovska ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Connexin 43 ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Spontaneously Hypertensive

Melatonin attenuates hypertension-related proarrhythmic myocardial maladaptation of connexin-43 and propensity of the heart to lethal arrhythmias

2013 ◽  
Vol 91 (8) ◽  
pp. 633-639 ◽  
Author(s):  
Tamara Benova ◽  
Csilla Viczenczova ◽  
Jana Radosinska ◽  
Barbara Bacova ◽  
Vladimir Knezl ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Wistar Rats ◽  
Electrical Coupling ◽  
Wistar Rat ◽  
Spontaneously Hypertensive ◽  
Kinase C ◽  
Rat Hearts ◽  
Cx43 Mrna ◽  
Cardioprotective Effects ◽  
Coupling Protein

We hypothesized that the pineal hormone melatonin, which exhibits cardioprotective effects, might affect myocardial expression of cell-to-cell electrical coupling protein connexin-43 (Cx43) and protein kinase C (PKC) signaling, and hence, the propensity of the heart to lethal ventricular fibrillation (VF). Spontaneously hypertensive (SHR) and normotensive Wistar rats fed a standard rat chow received melatonin (40 μg/mL in drinking water during the night) for 5 weeks, and were compared with untreated rats. Melatonin significantly reduced blood pressure and normalized triglycerides in SHR, whereas it decreased body mass and adiposity in Wistar rats. Compared with healthy rats, the threshold to induce sustained VF was significantly lower in SHR (18.3 ± 2.6 compared with 29.2 ± 5 mA; p < 0.05) and increased in melatonin-treated SHR and Wistar rats to 33.0 ± 4 and 32.5 ± 4 mA. Melatonin attenuated abnormal myocardial Cx43 distribution in SHR, and upregulated Cx43 mRNA, total Cx43 protein, and its functional phosphorylated forms in SHR, and to a lesser extent, in Wistar rat hearts. Moreover, melatonin suppressed myocardial proapoptotic PKCδ expression and increased cardioprotective PKCε expression in both SHR and Wistar rats. Our findings indicate that melatonin protects against lethal arrhythmias at least in part via upregulation of myocardial Cx43 and modulation of PKC-related cardioprotective signaling.

scholarly journals Omacor Protects Normotensive and Hypertensive Rats Exposed to Continuous Light from Increased Risk to Malignant Cardiac Arrhythmias

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 659
Author(s):  
Tamara Egan Benova ◽  
Csilla Viczenczova ◽  
Barbara Szeiffova Bacova ◽  
Jitka Zurmanova ◽  
Vladimir Knezl ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Electrical Coupling ◽  
Continuous Light ◽  
Male Rat ◽  
Human Populations ◽  
Omega 3 ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Populations At Risk ◽  
Increased Risk

Light pollution disturbs circadian rhythm, and this can also be deleterious to the heart by increased susceptibility to arrhythmias. Herein, we investigated if rats exposed to continuous light had altered myocardial gene transcripts and/or protein expression which affects arrhythmogenesis. We then assessed if Omacor® supplementation benefitted affected rats. Male and female spontaneously hypertensive (SHR) and normotensive Wistar rats (WR) were housed under standard 12 h/12 h light/dark cycles or exposed to 6-weeks continuous 300 lux light for 24 h. Half the rats were then treated with 200 mg/100 g b.w. Omacor®. Continuous light resulted in higher male rat vulnerability to malignant ventricular fibrillation (VF). This was linked with myocardial connexin-43 (Cx43) down-regulation and deteriorated intercellular electrical coupling, due in part to increased pro-inflammatory NF-κB and iNOS transcripts and decreased sarcoplasmic reticulum Ca2+ATPase transcripts. Omacor® treatment increased the electrical threshold to induce the VF linked with amelioration of myocardial Cx43 mRNA and Cx43 protein levels and the suppression of NF-κB and iNOS. This indicates that rat exposure to continuous light results in deleterious cardiac alterations jeopardizing intercellular Cx43 channel-mediated electrical communication, thereby increasing the risk of malignant arrhythmias. The adverse effects were attenuated by treatment with Omacor®, thus supporting its potential benefit and the relevance of monitoring omega-3 index in human populations at risk.

scholarly journals Modulation of Cardiac Connexin-43 by Omega-3 Fatty Acid Ethyl-Ester Supplementation Demonstrated in Spontaneously Diabetic Rats

2015 ◽  
pp. 795-806 ◽  
Author(s):  
J. RADOSINSKA ◽  
L. H. KURAHARA ◽  
K. HIRAISHI ◽  
C. VICZENCZOVA ◽  
T. EGAN BENOVA ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Connexin 43 ◽  
Early Stage ◽  
Acid Ethyl Ester ◽  
Diabetic Rats ◽  
Omega 3 ◽  
Omega 3 Fatty Acid ◽  
Pkc Delta ◽  
Pkc Epsilon ◽  
Spontaneously Diabetic Rats

Previous data suggest that type 1 diabetes mellitus leads to the deterioration of myocardial intercellular communication mediated by connexin-43 (Cx43) channels. We therefore aimed to explore Cx43, PKC signaling and ultrastructure in non-treated and omega-3 fatty acid (omega-3) treated spontaneously diabetic Goto-Kakizaki (GK) rats considered as type 2 diabetes model. Four-week-old GK and non-diabetic Wistar-Clea rats were fed omega-3 (200 mg/kg/day) for 2 months and compared with untreated rats. Real-time PCR and immunoblotting were performed to determine Cx43, PKC-epsilon and PKC-delta expression. In situ Cx43 was examined by immunohistochemistry and subcellular alterations by electron microscopy. Omega-3 intake reduced blood glucose, triglycerides, and cholesterol in diabetic rats and this was associated with improved integrity of cardiomyocytes and capillaries in the heart. Myocardial Cx43 mRNA and protein levels were higher in diabetic versus non-diabetic rats and were further enhanced by omega-3. The ratio of phosphorylated (functional) to non-phosphorylated Cx43 was lower in diabetic compared to non-diabetic rats but was increased by omega-3, in part due to up-regulation of PKC-epsilon. In addition, pro-apoptotic PKC-delta expression was decreased. In conclusion, spontaneously diabetic rats at an early stage of disease benefit from omega-3 intake due to its hypoglycemic effect, upregulation of myocardial Cx43, and preservation of cardiovascular ultrastructure. These findings indicates that supplementation of omega-3 may be beneficial also in the management of diabetes in humans.

Sign in / Sign up

Export Citation Format

Share Document