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Implication of adenylyl cyclase 8 in pathological smooth muscle cell migration occurring in rat and human vascular remodelling
Author(s) -
Gueguen Marie,
Keuylian Zela,
Mateo Véronique,
Mougenot Nathalie,
Lompré AnneMarie,
Michel JeanBaptiste,
Meilhac Olivier,
Lipskaia Larissa,
Limon Isabelle
Publication year - 2010
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2716
Subject(s) - vascular smooth muscle , restenosis , adenylyl cyclase , pathological , matrix metalloproteinase , cell , medicine , biology , endocrinology , pathology , smooth muscle , stimulation , stent , genetics
Recently, we discovered on primary cell cultures that adenylyl cyclase type 8 (AC8) was involved in the transition of rat vascular smooth muscle cells (VSMCs) to an inflammatory phenotype. Here we demonstrate, in human vessels displaying early or advanced atherosclerotic lesions, that: (a) only intimal VSMCs strongly express AC8; and (b) very few AC8‐positive VSMCs were detected in the medial layer, either in atherosclerotic or healthy arteries. Furthermore, over‐expressing AC8 in primary rat VSMC cultures triggered the recolonization of a wounded zone and similar results were obtained in the presence of mitomycin, a potent inhibitor of proliferation. This phenomenon was prevented by silencing AC8. Indeed, in IL‐1β‐treated cells, AC8 silencing halted migration and decreased the matrix‐metalloproteinases 2/9 secretion, known to be involved in VSMC migration. In vivo , we showed: (a) a pronounced up‐regulation of AC8 expression in highly migrating VSMCs of the injured rat carotid artery; (b) an undetectable AC8 labelling in re‐endothelized vessels where neo‐intimal thickening had stopped. From our data, we conclude that AC8 expression appears closely linked to the properties developed by VSMCs in atherosclerosis and post‐angioplasty neo‐intima formation leading to restenosis. In addition, it reinforces the idea that VSMC responses to their cell environment greatly depend on the AC isoforms expressed and attributes a new role for AC8 in these pathological vascular processes. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.