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Oxidized‐Phospholipids Alter Connexin Expression and Gap Junction Organization at the Myoendothelial Junction
Author(s) -
Isakson Brant E,
Kronke Gerhard,
Kadl Alexandra,
Duling Brian R,
Leitinger Norbert
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a634-a
Subject(s) - connexin , gap junction , microbiology and biotechnology , immunocytochemistry , biology , cell , chemistry , biophysics , biochemistry , endocrinology , intracellular
Previous work has shown altered connexin expression in endothelial cells (EC) and smooth muscle cells (SMC) found in atherosclerotic plaques, however the connexin expression and the gap junctions between the two cell types are unknown. One of the key factors in the initiation of atherosclerosis is lipoprotein‐derived oxidized‐phospholipids (OxPL). In an attempt to model atherosclerotic conditions, we applied OxPL to a vascular cell co‐culture (VCC). The VCC maintains compartmentalized layers of EC and SMC, with functional heterotypic gap junctions between the two cell types at the myoendothelial junction (MEJ; Isakson and Duling, Circ Res, 2005). OxPL was simultaneously applied to the EC and SMC. Immunoblots of EC demonstrated down‐regulation of Cx37 and Cx40 in a dose‐dependent manner. Connexin43 expression was slightly elevated. SMC connexins responded differently to OxPL; Cx37 and Cx40 were both increased in a dose‐dependant manner and again Cx43 expression was slightly elevated. En face immunocytochemistry of EC and SMC confirmed these results. To examine connexin expression at the MEJ, transverse sections from the VCC were used. After OxPL treatment, we found that Cx43 was the only connexin expressed at the MEJ. Biocytin dye transfer assays confirmed that the gap junctions between the two cells had shifted from heterotypic to homotypic Cx43. The change in gap junction organization would likely have significant effects on solute transfer. We conclude that OxPL induced changes in connexin expression would modify cell‐cell communication in the vessel wall.