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

Autor: Miroslav Barancik, Tamara Egan Benova, Matus Sykora, Jan Slezak, Hana Rauchová, Tomáš Soukup, Barbara Szeiffova Bacova, Weismann P, Stanislav Pavelka, Jitka Zurmanova, Narcis Tribulova, Lin Hai Kurahara
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
connexin-43
extracellular matrix
heart
030204 cardiovascular system & hematology
Rats
Inbred WKY
Article
Catalysis
lcsh:Chemistry
Inorganic Chemistry
Extracellular matrix
03 medical and health sciences
Basal (phylogenetics)
0302 clinical medicine
Rats
Inbred SHR
Internal medicine
medicine
Animals
cardiovascular diseases
Physical and Theoretical Chemistry
Protein kinase A
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
chemistry.chemical_classification
thyroid hormones
Extracellular Matrix Proteins
business.industry
Myocardium
Organic Chemistry
Thyroid
General Medicine
Computer Science Applications
030104 developmental biology
Endocrinology
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Connexin 43
Thyroid hormones
Hypertension
Phosphorylation
business
spontaneously hypertensive rats
Polyunsaturated fatty acid
Transforming growth factor
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 15
International Journal of Molecular Sciences, Vol 20, Iss 15, p 3758 (2019)
ISSN: 1422-0067
DOI: 10.3390/ijms20153758
Popis: 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 &beta
1 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.
Databáze: OpenAIRE
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