Flow loading induces macrophage antioxidative gene expression in experimental aneurysms

Takeshi K. Nakahashi, Katsuyuki Hoshina, Philip S. Tsao, Eiketsu Sho, Mien Sho, John K. Karwowski, Cory Yeh, Ruey Bing Yang, James N. Topper, Ronald L. Dalman

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Objective - Reactive oxygen species may act as proinflammatory mediators in abdominal. aortic aneurysm (AAA) disease. Flow loading increases antioxidative enzyme expression and limits reactive oxygen species production in vascular smooth muscle cells in vitro, limits experimental AAA enlargement in rodent models, and is indirectly associated with reduced clinical AAA risk. We attempted to determine the mechanism or mechanisms by which flow loading limits AAA enlargement. Methods and Results - Rodent AAAs were flow loaded via femoral arteriovenous fistula creation. Aortic wall shear stress and relative wall strain were significantly higher in flow-loaded rodents. Flow loading reduced AAA diameter by 26% despite evidence of flow-mediated aortic enlargement proximal to the aneurysmal segment. Messenger RNA from AAA tissue was harvested for cDNA labeling and hybridization to a 384-clone DNA microarray. Twenty-nine genes were differentlally differentially expressed (relative intensity/relative intensity of control ratio >1.5 and <0.67) in flow-loaded compared with normal flow AAA tissue, including heme oxygenase 1 (HO-1). Increased HO-1 expression was confirmed via reverse transcriptase-polymerase chain reaction. Immunohistochemistry localized HO-1 expression to infiltrative macrophages, α-Tocopherol was found to be as effective as flow loading in limiting AAA enlargement. Flow loading and α-tocopherol therapy reduced AAA reactive oxygen species production. Conclusions - Flow loading may attenuate AAA enlargement via wall shear or strain-related reductions in oxidative stress.

Original languageEnglish (US)
Pages (from-to)2017-2022
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2002

Keywords

  • Abdominal aortic aneurysm
  • Alpha-tocopherol
  • Heme oxygenase 1
  • Reactive oxygen species
  • Shear stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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