title: Interferon-beta attenuates angiotensin II-accelerated atherosclerosis and vascular remodeling in apolipoprotein E deficient mice.
abstract: Atherosclerotic vascular disease is an inflammatory disease. Interferon-beta (IFN-beta) is an important immune modulator. However, the role of IFN-beta in atherosclerotic vascular disease is still not clear. The present study is designed to determine the effects of IFN-beta on atherosclerosis, abdominal aortic aneurysm (AAA) formation and proliferative vascular remodeling in apolipoprotein E (apoE) deficient mice. Six-month-old male apoE deficient mice fed a normal chow underwent ligation of the common left carotid artery, and were randomly assigned to receive either vehicle or angiotensin II (Ang II, 1.4 mg/kg daily) via a subcutaneously implanted osmotic infusion pump. The animals were further assigned to groups that were subjected to subcutaneous injection of vehicle or murine IFN-beta (10 MIU/kg, daily). Ang II increased atherosclerotic area in the non-ligated carotid artery and aortic arch, induced AAA, and exacerbated ligation-induced adventitial proliferation and neointimal hyperplasia characterized by smooth muscle cell (SMC) proliferation and macrophage infiltration in the ligated carotid artery. Co-treatment with IFN-beta, had no effects by itself, significantly attenuated Ang II-accelerated increase in the areas of neointima, adventitia, SMC and macrophage in the ligated carotid artery and suppressed Ang II-exacerbated atherosclerosis, but did not affect Ang II-induced AAA formation. These data indicate that IFN-beta can play a prominent anti-atherosclerosis, anti-inflammation, and anti-proliferation role of vasculoprotection.
authors.affiliation: Department of Pharmacology and Immunology, Berlex Bioscience, 2600 Hilltop Drive, P.O. Box 4099, Richmond, CA 94806, USA. Le-Ning_Zhang@berlex.com
authors.forename: Le-Ning
authors.initials: LN
authors.lastname: Zhang
authors.forename: Sharlene
authors.initials: S
authors.lastname: Velichko
authors.forename: Jon
authors.initials: J
authors.lastname: Vincelette
authors.forename: Richard M
authors.initials: RM
authors.lastname: Fitch
authors.forename: Ronald
authors.initials: R
authors.lastname: Vergona
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sullivan
authors.forename: Ed
authors.initials: E
authors.lastname: Croze
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D005487:Foam Cells / Q000473:pathology; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D017539:Tunica Intima / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D001057:Apolipoproteins E; D007155:Immunologic Factors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016899:Interferon-beta