Omega-3 fatty acids (omega3FA) are known to reduce hypertriglyceridemia- and inflammation-induced vascular wall diseases. However, mechanisms of their effects are not completely clear. We examined, whether 10-day omega3FA diet can reduce bacterial lipopolysaccharide-induced changes in expression of gap junction protein connexin40 (Cx40) in the aorta of hereditary hypertriglyceridemic (hHTG) rats. After administration of a single dose of lipopolysaccharide (LPS, 1 mg/kg, i.p.) to adult hHTG rats, animals were fed with omega3FA diet (30 mg/kg/day) for 10 days. LPS decreased Cx40 expression that was associated with reduced acetylcholine-induced relaxation of aorta. Omega3FA administration to LPS rats had partial anti-inflammatory effects, associated with increased Cx40 expression and improved endothelium dependent relaxation of the aorta. Our results suggest that 10-day omega3FA diet could protect endothelium-dependent relaxation of the aorta of hHTG rats against LPS-induced damage through the modulation of endothelial Cx40 expression.
- MeSH
- antigeny diferenciační myelomonocytární metabolismus MeSH
- aorta účinky léků metabolismus MeSH
- CD antigeny metabolismus MeSH
- hypertriglyceridemie vrozené dietoterapie metabolismus MeSH
- konexiny metabolismus MeSH
- krysa rodu rattus MeSH
- kyseliny mastné omega-3 farmakologie terapeutické užití MeSH
- lipopolysacharidy MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- experimentální diabetes mellitus metabolismus patologie prevence a kontrola MeSH
- fixní kombinace léků MeSH
- konexin 43 metabolismus MeSH
- krysa rodu rattus MeSH
- kyselina eikosapentaenová farmakologie terapeutické užití MeSH
- kyseliny dokosahexaenové farmakologie terapeutické užití MeSH
- myokard metabolismus ultrastruktura MeSH
- potravní doplňky MeSH
- preklinické hodnocení léčiv MeSH
- proteinkinasa C-delta metabolismus MeSH
- proteinkinasa C-epsilon metabolismus MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- lidé MeSH
- teratologie * dějiny MeSH
- významné osobnosti * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
