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(Hypertension. 2009;54:1035.)
© 2009 American Heart Association, Inc.

Original Articles

Hepatocyte gp130 Deficiency Reduces Vascular Remodeling After Carotid Artery Ligation

Gustavo Salguero; Harald Schuett; Joanna Jagielska; René Schley; Ezequiel Tallone; Maren Luchtefeld; Helmut Drexler; Werner Müller; Karsten Grote; Bernhard Schieffer

From the Department of Cardiology and Angiology (G.S., H.S., J.J., R.S., E.T., M.L., H.D., K.G., B.S.), Hannover Medical School, Hannover, Germany; Faculty of Life Sciences (W.M.), Manchester University, Manchester, United Kingdom.

Correspondence to Bernhard Schieffer, Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Strasse 1, 30165 Hannover, Germany. E-mail Schieffer.Bernhard{at}mh-hannover.de

Inflammation and vascular remodeling are hallmarks of atherosclerosis, hypertension, and restenosis after angioplasty. Here we investigated the role of the hepatocyte gp130-dependent systemic acute phase response on vascular remodeling after carotid artery ligation. Mice with a hepatocyte-specific gp130 knockout on an apolipoprotein E^–/– background (gp130^–) were compared with control mice (gp130^flox). Vascular remodeling was induced by permanent ligation of the left common carotid artery. This, in turn, activated the systemic acute phase reaction in gp130^flox mice, as measured by serum amyloid A plasma levels, which was completely abrogated in gp130^– mice (P<0.05). Morphometric analysis of the carotid artery revealed severe neointima formation and media thickening 28 days after ligation in gp130^flox mice, which was suppressed in gp130^– mice (P<0.01). Serial sections from gp130^– carotid segments showed significantly less smooth muscle cell (SMC) proliferation and monocyte recruitment (P<0.01). To evaluate the impact of the gp130-dependent systemic acute phase response on SMCs, hepatocytes from gp130^flox and gp130^– mice were stimulated with interleukin 6. Interleukin 6–induced secretion of serum amyloid A was completely abolished in gp130^– hepatocytes (P<0.01). Moreover, when stimulated with supernatants from gp130^– hepatocytes, SMCs showed significantly less migration and proliferation compared with supernatants from gp130^flox hepatocytes (P<0.01). Recombinant serum amyloid A induced SMC migration and proliferation (P<0.05) and serum amyloid A injection after carotid artery ligation restored vascular remodeling in gp130^– mice (P<0.01). These results imply a critical role for the gp130-dependent systemic acute phase response for vascular inflammation and SMC migration, as well as proliferation, and, subsequently, for vascular remodeling.

Key Words: vascular remodeling • gp130 • acute phase reaction • SMC migration/proliferation