Deletion of the NR4A Nuclear Receptor NOR1 in Hematopoietic Stem Cells Reduces Inflammation but Not Abdominal Aortic Aneurysm Formation
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.
Digital Object Identifier (DOI)
This work was supported in part by National Institutes of Health Grants (R01HL084611, R01HL084611-04S1, and R01HL111040 to D.B.) and the American Heart Association (15PRE24480143 to H. Q.).
All original source datasets and measurements used to generate figures in the current study are available from the corresponding author on request.
Qing, Hua; Jones, Karrie L.; Heywood, Elizabeth B.; Lu, Hong; Daugherty, Alan; and Bruemmer, Dennis, "Deletion of the NR4A Nuclear Receptor NOR1 in Hematopoietic Stem Cells Reduces Inflammation but Not Abdominal Aortic Aneurysm Formation" (2017). Pharmacology and Nutritional Sciences Faculty Publications. 51.
Additional file 1: Table S1.
12872_2017_701_MOESM2_ESM.pdf (22 kB)
Additional file 2: Table S2.
Cardiology Commons, Medical Nutrition Commons, Medical Pharmacology Commons, Pharmacology, Toxicology and Environmental Health Commons, Physiology Commons
Published in BMC Cardiovascular Disorders, v. 17, 271, p. 1-9.
© The Author(s). 2017
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.