Cell-cell bond modulates vascular smooth muscle cell responsiveness to Angiotensin II.
Cell attachment is provided by cell-matrix and cell-cell bonds, and acts as a regulator of vascular smooth muscle cell (VSMC) survival, activity and homeostasis, as well as of VSMCs response to pathogenic stimuli. In this work we elicited an exclusive cell-cell contact by culturing A7r5 VSMCs on agarose-coated wells to form floating cell clusters, and we demonstrated that a steady state with a reduced response to the vasoactive peptide Angiotensin II (ATII) was induced. We found that clustered VSMCs showed subcortical stabilization of beta-catenin and Caveolin 1 (Cav1), unlike adherent confluent counterparts. We demonstrated that beta-catenin and Cav1 stabilization at the membrane level hampers the molecular cross-talk induced by ATII-activated AT1 receptor (AT1R), thereby impeding the phosphorylation of Cav1 and IGF1R, the NADPH oxidase activity, and counteracting ATII-dependent hypertrophy. Thus, elective cell-cell bond might modulate the proatherogenic activity of ATII, reducing the adverse vascular remodelling associated with AT1R activation.
Barisione
Chiara
C
Division of Cardiology, Department of Internal Medicine, Research Center of Cardiovascular Biology, University of Genova, Viale Benedetto XV, 6, Genova 16132, Italy. cbari@libero.it
Mura
Marzia
M
Garibaldi
Silvano
S
Fabbi
Patrizia
P
Altieri
Paola
P
Passalacqua
Mario
M
Salani
Barbara
B
Ghigliotti
Giorgio
G
Aloi
Concetta
C
Spallarossa
Paolo
P
Brunelli
Claudio
C
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D049109:Cell Proliferation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019255:NADPH Oxidases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D051242:Caveolin 1; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D051176:beta Catenin; D000804:Angiotensin II; D019255:NADPH Oxidases; D017526:Receptor, IGF Type 1