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 ◽  
...  

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.

2016 ◽  
pp. S77-S90 ◽  
Author(s):  
B. SZEIFFOVÁ BAČOVÁ ◽  
T. EGAN BEŇOVÁ ◽  
C. VICZENCZOVÁ ◽  
T. SOUKUP ◽  
H. RAUCHOVÁ ◽  
...  

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.


2010 ◽  
Vol 347 (1-2) ◽  
pp. 163-173 ◽  
Author(s):  
Jana Radosinska ◽  
Barbara Bacova ◽  
Iveta Bernatova ◽  
Jana Navarova ◽  
Anna Zhukovska ◽  
...  

2008 ◽  
pp. S39-S48
Author(s):  
M Mitašíková ◽  
S Šmidová ◽  
A Macsaliová ◽  
V Knezl ◽  
K Dlugošová ◽  
...  

Hypertension-induced myocardial metabolic, structural and electrophysiological remodeling deteriorates with aging and contributes to both heart failure and occurrence of malignant arrhythmias. It has been shown in clinical trials that n-3 polyunsaturated fatty acids (n-3 PUFA) reduce the incidence of cardiovascular diseases and sudden cardiac death. We investigated the cardioprotective effects of n-3 PUFA in aged spontaneously hypertensive rats (SHR) and possible cellular mechanisms involved. Male and female 14-moth-old SHR were fed with n-3 PUFA (Vesteralens, Norway, 20 mg/day for two months) and compared with untreated SHR. Results showed that n-3 PUFA supplementation led to 1) significant decline of blood pressure; 2) suppression of inducible ventricular fibrillation (VF) by 57 % (male) and 67 % (female), although the arrhythmogenic substrates, like fibrosis, hypertrophy and abnormal gap junctions distribution were not eliminated; 3) preservation of the cardiomyocytes and the integrity of their junctions; 4) enhancement of energetic metabolism enzyme activity; 5) augmentation of capillary density associated with increased alkaline phosphatase and decreased dipeptidyl peptidase-4 (DPP4) activity and 6/ increase in gap junction channel connexin-43 expression. Thus, aged male as well as female SHR benefit from n-3 PUFA supplementation that results in decrease in VF susceptibility, partly due to an improvement of myocardial metabolic state, cardiomyocyte and cell-to-cell junctions integrity and Cx43 up-regulation.


2013 ◽  
Vol 45 (07) ◽  
pp. 507-512 ◽  
Author(s):  
H. Rauchová ◽  
M. Vokurková ◽  
S. Pavelka ◽  
M. Behuliak ◽  
N. Tribulová ◽  
...  

2020 ◽  
Vol 36 (2) ◽  
pp. 95-106
Author(s):  
Agnieszka M. Piróg-Balcerzak ◽  
Anna K. Bażyńska ◽  
Katarzyna Biernacka ◽  
Joanna Brągoszewska ◽  
Lidia Popek ◽  
...  

Objective. Omega–3 polyunsaturated fatty acids (PUFAs) were tested in adolescent depression and in several neurodevelopmental disorders with partial success. Anorexia nervosa (AN) is characterised by deficiencies in fatty food intake and frequent comorbidity, including depressive and cognitive symptoms. Thus supplementation with PUFAs may be beneficial in this group of patients. The aim of the study was to assess whether PUFAs as an add-on treatment is associated with better improvement of body mass index (BMI) and psychopathological symptoms than placebo in patients with AN. Method. 61 female adolescent inpatients with AN were randomly allocated to omega–3 PUFAs supplementation or placebo for 10 weeks. Patients also participated in the behavioural programme and eclectic psychotherapy (treatment as usual, TAU). At baseline and follow-up visits, patients’ BMI and psychopathology were assessed with Clinical Global Impression Scale (CGI), Patient Global Impression Scale (PGI), and Eating Attitude Test (EAT-26). Results. After 10 weeks, both groups showed improvement in all parameters. Improvement in CGI scores was observed greater in placebo vs. PUFA-s group (p = 0.015) while other differences were not statistically significant. Omega–3 PUFAs supplementation appears not to be effective as an add-on treatment in inpatient adolescent girls with anorexia nervosa. Conclusions. The results should be analysed with caution due to small sample size and heterogeneity in TAU. As the TAU turned out to be highly effective, additional therapeutic effect of PUFA might not be visible. Nevertheless, that does not explain the tendency for better improvement in the placebo group.


2013 ◽  
Vol 13 (8) ◽  
pp. 1162-1177 ◽  
Author(s):  
Kaipeng Jing ◽  
Tong Wu ◽  
Kyu Lim

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