Impact of IL-1beta on flow-induced outward arterial remodeling.
BACKGROUND
Flow reduction upregulates arterial wall interleukin 1beta (IL-1beta), and IL-1beta independently modulates intimal hyperplasia under low flow conditions. We hypothesized that IL-1beta expression is also augmented under high flow, and outward remodeling occurs by way of IL-1beta-dependent mechanisms.


METHODS
Carotid artery (CA) flow was surgically augmented in rabbits (n = 20). CAs were harvested at 1, 3, 7, and 14 days, and assayed via quantitative reverse transcriptase-polymerase chain reaction. IL-1 receptor I null mice (KO) and wild-type controls underwent unilateral CA ligation and harvest 4 weeks later to assess the impact of increased flow on the contralateral CA (n = 82).


RESULTS
The rabbit model led to an immediate 36% increase in contralateral flow (P = .01) with an 80% increase at 14 days (P = .016) with subsequent positive remodeling. High flow induced IL-1beta messenger RNA expression (114-fold at 1 day, P < .05), with levels remaining elevated through 14 days (61-fold, P < .05). In murine experiments, CA ligation resulted in a 44% increase in contralateral flow. Wild-type and KO animals responded with equivalent 83% and 78% increases in luminal area (P = .87).


CONCLUSIONS
Positive and negative perturbations of arterial blood flow induce IL-1beta in a time-dependent fashion. However, as opposed to intimal hyperplasia after flow reduction, positive arterial remodeling in response to increased flow occurs via IL-1beta independent mechanisms.
University of Florida College of Medicine and the Malcom Randall VAMC, Gainesville, FL, USA.
Zhihua
Z
Jiang
Scott A
SA
Berceli
Chun L
CL
Pfahnl
Lizhen
L
Wu
Chris D
CD
Killingsworth
Fernando G
FG
Vieira
C Keith
CK
Ozaki
D000818:Animals; D002339:Carotid Arteries / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012039:Regional Blood Flow
D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1