Impact of IL-1beta on flow-induced outward arterial remodeling

Surgery. 2004 Aug;136(2):478-82. doi: 10.1016/j.surg.2004.05.028.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carotid Arteries / physiology*
  • Interleukin-1 / physiology*
  • Male
  • Mice
  • RNA, Messenger / analysis
  • Rabbits
  • Receptors, Interleukin-1 / physiology
  • Regional Blood Flow

Substances

  • Interleukin-1
  • RNA, Messenger
  • Receptors, Interleukin-1