Interferon-beta attenuates angiotensin II-accelerated atherosclerosis and vascular remodeling in apolipoprotein E deficient mice.
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.
Zhang
Le-Ning
LN
Department of Pharmacology and Immunology, Berlex Bioscience, 2600 Hilltop Drive, P.O. Box 4099, Richmond, CA 94806, USA. Le-Ning_Zhang@berlex.com
Velichko
Sharlene
S
Vincelette
Jon
J
Fitch
Richard M
RM
Vergona
Ronald
R
Sullivan
Mark E
ME
Croze
Ed
E
Wang
Yi-Xin
YX
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*
D001057:Apolipoproteins E; D007155:Immunologic Factors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016899:Interferon-beta