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.

• Keywords
• connexin-43, extracellular matrix, heart, spontaneously hypertensive rats, thyroid hormones,
• MeSH
• Extracellular Matrix Proteins metabolism   MeSH
• Thyroid Hormones blood   metabolism   MeSH
• Hypertension blood   metabolism   MeSH
• Connexin 43 metabolism   MeSH
• Myocardium metabolism   MeSH
• Rats, Inbred SHR MeSH
• Rats, Inbred WKY MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Extracellular Matrix Proteins MeSH
• Gja1 protein, rat MeSH Browser
• Thyroid Hormones MeSH
• Connexin 43 MeSH

We aimed to study the impact of altered thyroid status on myocardial expression of electrical coupling protein connexin-43 (Cx43), the susceptibility of rats to ventricular fibrillation (VF) and the effects of antioxidant-rich red palm oil (RPO). Adult male and female euthyroid, hyperthyroid (treated with T3/T4), hypothyroid (treated with methimazole) Wistar rats supplemented or not with RPO for 6 weeks were used. Function of isolated perfused heart and VF threshold were determined. Left ventricular tissue was used for assessment of mRNA and protein levels of Cx43, its phosphorylated forms and topology. Protein kinase C signaling (PKC) and gene transcripts of some proteins related to cardiac arrhythmias were assessed. Hyperthyroid state resulted in decrease of total and phosphorylated forms of Cx43 and suppression of PKC-ε expression in males and females, decrease of Cx43 mRNA in females, decrease of VF threshold and increase of functional parameters in male rat hearts. In contrast, hypothyroid status resulted in the increase of total and phosphorylated forms of Cx43, enhancement PKC-ε expression in males and females, increase of Cx43 mRNA in females, increase of VF threshold and decrease of functional parameters in male rat hearts. Function of the heart was partially normalized by RPO intake, which also enhanced myocardial Cx43 and PKC-ε expression as well as increased VF threshold in hyperthyroid male rats. We conclude that there is an inverse relationship between myocardial expression of Cx43, including its functional phosphorylated forms, and susceptibility of male rat hearts to VF in condition of altered thyroid status. RPO intake partly ameliorated adverse changes caused by excess of thyroid hormones.

• Keywords
• Cardiac arrhythmias, Connexin-43, PKC, Red palm oil, Thyroid hormones,
• MeSH
• Administration, Oral MeSH
• Connexin 43 antagonists & inhibitors   genetics   metabolism   MeSH
• Rats MeSH
• RNA, Messenger antagonists & inhibitors   genetics   metabolism   MeSH
• Myocardium metabolism   MeSH
• Plant Oils administration & dosage   pharmacology   MeSH
• Palm Oil MeSH
• Rats, Wistar MeSH
• Heart drug effects   MeSH
• Arrhythmias, Cardiac drug therapy   metabolism   MeSH
• Thyroid Gland drug effects   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Gja1 protein, rat MeSH Browser
• Connexin 43 MeSH
• RNA, Messenger MeSH
• Plant Oils MeSH
• Palm Oil MeSH

In this mini-review, we briefly present the data regarding the effect of extrinsic factors, i.e., innervation and thyroid hormones (TH) on myosin heavy chain genes and isoforms expression and consequently on muscle fiber type transitions. It has been well known that reduced neuromuscular activity, hyperthyroidism or mechanical unloading stimulate slow-to-fast fiber type transitions, while increased neuromuscular activity, hypothyroidism and higher mechanical loading result in fast to slow fiber type transitions. As there is a plethora of results on these topics, we focus mostly on data relevant to our experimental model of slow-to-fast muscle transformation following heterochronous intramuscular isotransplantation in rats with altered TH status.

• MeSH
• Thyroid Hormones metabolism   pharmacology   MeSH
• Rats MeSH
• Protein Isoforms metabolism   MeSH
• Gene Expression Regulation drug effects   physiology   MeSH
• Myosin Heavy Chains genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Thyroid Hormones MeSH
• Protein Isoforms MeSH
• Myosin Heavy Chains MeSH

We studied the effect of regeneration, altered innervation and thyroid hormone (TH) levels on fiber type transitions in slow soleus (SOL) muscles grafted (GRAFT) into host extensor digitorum longus (EDLh) muscles of euthyroid (EU), hyperthyroid (HT) and hypothyroid (HY) Lewis strain rats. SOL muscles were excised from 3-week to 4-week-old inbred Lewis rats and intramuscularly transplanted into EDLh muscles of 2-month-old female rats of the same strain. The proportions of type 1, 2A, 2X and 2B fibers of GRAFT were determined by immunohistochemistry and compared with those of EDLh muscle and EDL and SOL muscles of the unoperated contralateral hind limb. After an average regeneration period of 6-7 months and after being reinnervated by the "fast" peroneal nerve of EDLh muscle, GRAFT was transformed into a fast muscle. However, the extent of GRAFT transformation varied with different TH states. In the EU rats, GRAFT contained about 95 % of fast fibers, among which type 2X and 2B fibers predominated (about 75 %). The transition toward fast muscle phenotype was more pronounced in HT status, where the fastest type 2B fibers predominated. On the contrary, in HY status, the slow to fast transformation was less pronounced, as GRAFT contained less type 2B and 2X but more type 2A and 1 fibers. We conclude that the type of innervation is the crucial factor for the slow to fast fiber type transitions in GRAFT, but the extent of muscle transformation is further modulated by altered TH status.

• MeSH
• Time Factors MeSH
• Thyroid Hormones chemistry   metabolism   MeSH
• Muscle, Skeletal cytology   metabolism   transplantation   MeSH
• Rats MeSH
• Rats, Inbred Lew MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Thyroid Hormones MeSH