Reduced Expression of Endothelial Connexin37 and Connexin40 in Hyperlipidemic Mice: Recovery of Connexin37 After 7-Day Simvastatin Treatment

OBJECTIVE—We sought to clarify the response of endothelial connexins to hyperlipidemia and lipid-lowering therapy. METHODS AND RESULTS—Aortic endothelial gap junctions were analyzed by en face immunoconfocal microscopy and electron microscopy in C57BL/6 mice subjected to the following regimens(1) normal chow (NC) for 3 months (3 mo), (2) NC for 9 mo, (3) NC for 3 mo, followed by a cholesterol-enriched diet (CED) for 6 mo, (4) NC for 3 mo and CED for 6 mo, with simvastatin in the final week, and (5) (in apoprotein E [apoE]-deficient mice) NC and examined at 3 mo and 7 to 9 mo. In wild-type mice, connexin37 (Cx37) and Cx40 were markedly downregulated in the CED-fed animals compared with those fed NC (CED vs 9-mo NC, 77% reduction in Cx37 and 65% reduction in Cx40; both P