Oxidized phospholipids alter vascular connexin expression, phosphorylation, and heterocellular communication.
OBJECTIVE
In endothelial cells (EC) and vascular smooth muscle cells (VSMC) from atherosclerotic mice, connexin (Cx) expression becomes distorted. Lipoprotein-derived phospholipid oxidation products (OxPAPC) play a critical role in atherosclerosis, and we hypothesized that they may act as trigger molecules causing the changes in connexin expression.


RESULTS
We applied OxPAPC to murine carotid arteries in vivo and vascular cell cocultures. OxPAPC applied to carotids induced an upregulation of both Cx37 and Cx43 in the VSMC. In EC, Cx43 was upregulated and Cx37 was downregulated, whereas Cx40 in EC remained constant. In the vascular cell coculture, OxPAPC caused similar changes in Cx37 and Cx43 but caused a decrease in Cx40 in EC and an elevation of Cx40 in VSMC. In the coculture model, OxPAPC treatment led to the selective disappearance of Cx40 at the myoendothelial junction. Biocytin dye transfer between EC and VSMC coupling was dramatically reduced by OxPAPC. The decrease in dye transfer after OxPAPC treatment was correlated with an increase in tyrosine 265 phosphorylation of Cx43, especially at the in vitro myoendothelial junction.


CONCLUSIONS
We conclude that OxPAPC could be responsible for the changes in connexin expression previously reported in atherosclerosis.
Isakson
Brant E
BE
Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. bei6n@virginia.edu
Kronke
Gerhard
G
Kadl
Alexandra
A
Leitinger
Norbert
N
Duling
Brian R
BR
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010766:Phosphorylation; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
D018031:Connexin 43; D017630:Connexins; D008239:Lysine; D010713:Phosphatidylcholines; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein; C472349:oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine; C013411:biocytin