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BMC Cardiovasc Disord. 2017 Oct 18;17(1):271. doi: 10.1186/s12872-017-0701-4.

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

Qing H1,2,3,4, Jones KL4, Heywood EB4, Lu H2,4,5, Daugherty A2,4,5, Bruemmer D6,7,8.

Author information

1
Department of Medicine, Division of Cardiology, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, UPMC and University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
2
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY, 40536, USA.
3
Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
4
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, 40536, USA.
5
Department of Physiology, University of Kentucky, Lexington, KY, 40536, USA.
6
Department of Medicine, Division of Cardiology, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, UPMC and University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA. bruemmerd@upmc.edu.
7
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY, 40536, USA. bruemmerd@upmc.edu.
8
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, 40536, USA. bruemmerd@upmc.edu.

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.

KEYWORDS:

Aneurysm; Angiotensin II; Bone marrow transplantation; Nuclear receptor

PMID:
29047330
PMCID:
PMC5648424
DOI:
10.1186/s12872-017-0701-4
[Indexed for MEDLINE]
Free PMC Article

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