Deletion of the NR4A nuclear receptor NOR1 in hematopoietic stem cells reduces inflammation but not abdominal aortic aneurysm formation.

Abstract:

BACKGROUND:The NR4A3 orphan nuclear hormone receptor, NOR1, functions as a constitutively active transcription factor to regulate inflammation, proliferation, and cell survival during pathological vascular remodeling. Inflammatory processes represent key mechanisms leading to abdominal aortic aneurysm (AAA) formation. However, a role of NOR1 in AAA formation has not been investigated previously. METHODS:Inflammatory gene expression was analyzed in bone marrow-derived macrophages isolated from NOR1-deficient mice. Low-density lipoprotein receptor-deficient (LDLr-/-) mice were irradiated and reconstituted with hematopoietic stem cells obtained from NOR1-/- or wild-type littermate mice. Animals were infused with angiotensin II and fed a diet enriched in saturated fat to induce AAA formation. Quantification of AAA formation was performed by ultrasound and ex vivo measurements. RESULTS:Among 184 inflammatory genes that were analyzed, 36 genes were differentially regulated in LPS-treated NOR1-deficient macrophages. Albeit this difference in gene regulation, NOR1-deficiency in hematopoietic stem cells did not affect development of AAA formation in bone marrow-derived stem cell transplanted LDLr-deficient mice. CONCLUSION:NOR1 deletion induced differential inflammatory gene transcription in macrophages but did not influence AAA formation in mice.

journal_name

BMC Cardiovasc Disord

authors

Qing H,Jones KL,Heywood EB,Lu H,Daugherty A,Bruemmer D

doi

10.1186/s12872-017-0701-4

subject

Has Abstract

pub_date

2017-10-18 00:00:00

pages

271

issue

1

issn

1471-2261

pii

10.1186/s12872-017-0701-4

journal_volume

17

pub_type

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