MyD88 deficiency attenuates angiotensin II-induced abdominal aortic aneurysm formation independent of signaling through toll-like receptors 2 and 4

A. Phillip Owens, Debra L. Rateri, Deborah A. Howatt, Kathryn J. Moore, Peter S. Tobias, Linda K. Curtiss, Hong Lu, Lisa A. Cassis, Alan Daugherty

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Objective-The purpose of this study was to determine whether myeloid differentiation factor 88 (MyD88) and its related Toll-like receptors (TLRs) 2 and 4 contributed to the development of angiotensin II (AngII)-induced abdominal aortic aneurysms (AAAs) and atherosclerosis. Methods and results-AngII was infused into either apoE -/- or LDL receptor (LDLR) -/- male mice that were either MyD88 +/+ or -/- . MyD88 deficiency profoundly reduced AngII-induced AAAs and atherosclerosis in both strains. To define whether deficiency of specific TLRs had similar effects, AngII was infused into LDLR -/- mice that were also deficient in either TLR2 or TLR4. TLR2 deficiency had no effect on AAA development but inhibited atherosclerosis. In contrast, TLR4 deficiency attenuated both AAAs and atherosclerosis. To resolve whether MyD88 and TLR4 exerted their effects through cells of hematopoietic lineage, LDLR -/- mice were lethally irradiated and repopulated with bone marrow-derived cells from either MyD88 or TLR4 strains. MyD88 deficiency in bone marrow-derived cells profoundly reduced both AngII-induced AAAs and atherosclerosis. However, TLR4 deficiency in bone marrow-derived cells had no effect on either pathology. Conclusion-These studies demonstrate that MyD88 deficiency in leukocytes profoundly reduces AngII-induced AAAs and atherosclerosis via mechanisms independent of either TLR2 or TLR4.

Original languageEnglish
Pages (from-to)2813-2819
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number12
DOIs
StatePublished - Dec 2011

Keywords

  • aneurysms
  • angiotensin II
  • atherosclerosis
  • myeloid differentiation factor 88
  • toll-like receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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