Hepatocyte gp130 deficiency reduces vascular remodeling after carotid artery ligation

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Medicine

Background:

• Vascular remodeling, inflammation, and the acute phase response are key in atherosclerosis, hypertension, and post-angioplasty restenosis.
• The role of hepatocyte-specific gp130 signaling in these processes remains incompletely understood.

Purpose of the Study:

• To investigate the impact of hepatocyte gp130-dependent systemic acute phase response on vascular remodeling following carotid artery ligation.
• To elucidate the mechanisms by which this response influences vascular cell behavior.

Main Methods:

• Comparison of hepatocyte-specific gp130 knockout mice (gp130-) with control mice (gp130(flox)) on an apolipoprotein E(-/-) background.
• Induction of vascular remodeling via permanent carotid artery ligation.
• Assessment of systemic acute phase reaction (serum amyloid A levels), neointima formation, media thickening, smooth muscle cell (SMC) proliferation, and monocyte recruitment.
• In vitro stimulation of hepatocytes and SMCs with interleukin 6 and serum amyloid A.

Main Results:

• Carotid artery ligation induced a systemic acute phase reaction in control mice, which was abolished in gp130- mice.
• gp130- mice exhibited significantly suppressed neointima formation, media thickening, SMC proliferation, and monocyte recruitment post-ligation.
• Hepatocyte-specific gp130 knockout abrogated interleukin 6-induced serum amyloid A secretion.
• Serum amyloid A directly induced SMC migration and proliferation, and its administration restored vascular remodeling in gp130- mice.

Conclusions:

• The hepatocyte gp130-dependent systemic acute phase response critically mediates vascular inflammation and remodeling.
• Serum amyloid A, induced by this pathway, promotes SMC proliferation and migration, contributing to neointima formation.
• Targeting this hepatocyte-driven pathway may offer therapeutic strategies for vascular diseases.