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.


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<0.01). After simvastatin treatment, Cx40 remained depressed, but Cx37 recovered to 94% of the level found in non-cholesterol-fed animals (P<0.01). Electron microscopy demonstrated that gap junctions were smaller in animals fed the CED compared with those given simvastatin and with controls fed NC (P<0.01). Endothelial connexins were rare in the atherosclerotic plaques of apoE-deficient mice.


CONCLUSIONS
Mouse aortic endothelial gap junctions and connexins are downregulated during long-term hyperlipidemia. Short-term treatment with simvastatin leads to recovery of Cx37 expression but not Cx40 expression.
Yeh
Hung-I
HI
Mackay Memorial Hospital, Mackay Junior College of Nursing, Taipei Medical University, Taipei, Taiwan.
Lu
Chi-Sheng
CS
Wu
Yih-Jer
YJ
Chen
Chih-Chun
CC
Hong
Ray-Ching
RC
Ko
Yu-Shien
YS
Shiao
Ming-Shi
MS
Severs
Nicholas J
NJ
Tsai
Cheng-Ho
CH
D000818:Animals; D001011:Aorta / Q000473:pathology; D017630:Connexins / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D017629:Gap Junctions / Q000378:metabolism / Q000648:ultrastructure; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D019821:Simvastatin / Q000008:administration & dosage*; D014018:Tissue Distribution; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
D017630:Connexins; D019821:Simvastatin; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein