Deletion of hypoxia-inducible factor-1a in myeloid lineage exaggerates angiotensin II-induced formation of abdominal aortic aneurysm

Yusuke Takahara, Tomotake Tokunou, Hiroshi Kojima, Yoshitaka Hirooka, Toshihiro Ichiki

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7 Citations (Scopus)

Abstract

Hypoxia-inducible factor (HIF)-1A is a transcription factor that regulates various genes responding to hypoxic conditions. We previously reported that myeloid-specific activation of HIF-1A had protective effects on hypertensive cardiovascular remodelling in mice. However the role of myeloid lineage HIF-1A in the development of abdominal aortic aneurysm (AAA) has not been determined. Myeloid-specific HIF-1A knockout (HIF-1KO) mice were created using a Cre-lox recombination system in the background of apolipoprotein E-deficient (ApoE -/- ) mice. HIF-1KO and control mice were fed high-fat diet (HFD) and infused with angiotensin II (Ang II, 1800 ng/kg/min) by an osmotic mini pump for 4 weeks to induce AAA formation. Deletion of HIF-1A increased aortic external diameter (2.47± 0.21 mm versus 1.80± 0.28 mm in control, P= 0.035). AAA formation rate (94.4% in HIF-1KO versus 81.8% in control) was not statistically significant. Elastic lamina degradation grade determined by Elastica van Gieson (EVG) staining was deteriorated in HIF-1KO mice (3.91± 0.08 versus 3.25± 0.31 in control, P= 0.013). The number of infiltrated macrophages into the abdominal aorta was increased in HIF-1KO mice. Expression of tissue inhibitors of metalloproteinases (TIMPs) was suppressed in the aorta and peritoneal macrophages (PMs) from HIF-1KO mice compared with control mice. HIF-1A in myeloid lineage cells may have a protective role against AAA formation induced by Ang II and HFD in ApoE -/- mice.

Original languageEnglish
Pages (from-to)609-620
Number of pages12
JournalClinical Science
Volume131
Issue number7
DOIs
Publication statusPublished - Apr 1 2017

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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