Omega-3 fatty acids and atorvastatin affect connexin 43 expression in the aorta of hereditary hypertriglyceridemic rats.
Statins and omega-3 polyunsaturated fatty acids (n-3 PUFA) reduce cardiovascular disease incidence during hypertriglyceridemia (HTG). To elucidate possible cardioprotective mechanisms, we focused on gap junction protein connexin 43 (Cx43). Its expression is disturbed during atherogenesis, but little information is available on its expression during HTG. Experiments were performed on adult male hereditary HTG (hHTG) rats treated with n-3 PUFA (30 mg/day) and atorvastatin (0.5 mg/100 g body weight per day) for 2 months. Cx43 expression and distribution in the aorta were investigated by using Western blotting and immunolabeling, followed by quantitative analysis. Transmission electronmicroscopy was used to study ultrastructure of endothelial contact sites. In contrast to age-matched Wistar, Cx43 expression in aorta of hHTG rats was significantly higher (p < 0.05), and prominent Cx43 immunospots were seen in tunica media and less in endothelium of hHTG rats. Changes in Cx43 expression were accompanied by local qualitative subcellular alterations of interendothelial connections. Treatment of hHTG rats with n-3 PUFA and atorvastatin markedly lowered Cx43 expression in aorta and modified connexin distribution in endothelium and media (p < 0.05 vs. untreated hHTG). The protective effect of treatment of HTG was observed on the structural integrity of the endothelium and was readily visible at the molecular level. Results indicate the involvement of altered Cx43 expression in vascular pathophysiology during HTG and during HTG treatment.
Dlugosová
Katarína
K
Institute for Heart Research, Slovak Academy of Sciences, 840 05 Bratislava, Slovak Republic.
Weismann
Peter
P
Bernátová
Iveta
I
Sotníková
Ruzena
R
Slezák
Ján
J
Okruhlicová
Ludmila
L
D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D000069059:Atorvastatin; D015153:Blotting, Western; D018031:Connexin 43 / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D004730:Endothelium, Vascular / Q000648:ultrastructure; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015228:Hypertriglyceridemia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D018031:Connexin 43; D015525:Fatty Acids, Omega-3; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin