Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/89772
Title: Cyclooxygenase-2 selectively controls renal blood flow through a novel pparβ/δ-dependent vasodilator pathway
Authors: Shala, Fisnik
Nair, Anitha S.
Ahmetaj-Shala, Blerina
Jiao, Jing
Kirkby, Nicholas S.
Sampaio, Walkyria
Etelvino, Gisele
Alves, Daniele T.
Anders, Katie L.
Temponi, Rafael
Herschman, Harvey R.
Wang, Xiaomeng
Wahli, Walter
Santos, Robson A.
Mitchell, Jane A.
Keywords: Endothelium
Cyclooxygenase 2
DRNTU::Science::Medicine
Issue Date: 2018
Source: Kirkby, N. S., Sampaio, W., Etelvino, G., Alves, D. T., Anders, K. L., Temponi, R., . . . Mitchell, J. A. (2018). Cyclooxygenase-2 Selectively Controls Renal Blood Flow Through a Novel PPARβ/δ-Dependent Vasodilator Pathway. Hypertension, 71(2), 297-305. doi:10.1161/HYPERTENSIONAHA.117.09906
Series/Report no.: Hypertension
Abstract: Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in inflammation and cancer targeted by nonsteroidal anti-inflammatory drugs. COX-2 is also expressed constitutively in discreet locations where its inhibition drives gastrointestinal and cardiovascular/renal side effects. Constitutive COX-2 expression in the kidney regulates renal function and blood flow; however, the global relevance of the kidney versus other tissues to COX-2–dependent blood flow regulation is not known. Here, we used a microsphere deposition technique and pharmacological COX-2 inhibition to map the contribution of COX-2 to regional blood flow in mice and compared this to COX-2 expression patterns using luciferase reporter mice. Across all tissues studied, COX-2 inhibition altered blood flow predominantly in the kidney, with some effects also seen in the spleen, adipose, and testes. Of these sites, only the kidney displayed appreciable local COX-2 expression. As the main site where COX-2 regulates blood flow, we next analyzed the pathways involved in kidney vascular responses using a novel technique of video imaging small arteries in living tissue slices. We found that the protective effect of COX-2 on renal vascular function was associated with prostacyclin signaling through PPARβ/δ (peroxisome proliferator-activated receptor-β/δ). These data demonstrate the kidney as the principle site in the body where local COX-2 controls blood flow and identifies a previously unreported PPARβ/δ-mediated renal vasodilator pathway as the mechanism. These findings have direct relevance to the renal and cardiovascular side effects of drugs that inhibit COX-2, as well as the potential of the COX-2/prostacyclin/PPARβ/δ axis as a therapeutic target in renal disease.
URI: https://hdl.handle.net/10356/89772
http://hdl.handle.net/10220/46357
ISSN: 0194-911X
DOI: 10.1161/HYPERTENSIONAHA.117.09906
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2018 The Authors. Hypertension is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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