Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice

The anti-inflammatory properties of PPAR-α plays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-α agonist during a slow-pressor dose of Ang II (400 ng/kg/min). Ten to twelve week old male PPAR-α KO mice and their W...

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Main Authors: Justin L. Wilson, Rong Duan, Ahmed El-Marakby, Abdulmohsin Alhashim, Dexter L. Lee
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2012/645969
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author Justin L. Wilson
Rong Duan
Ahmed El-Marakby
Abdulmohsin Alhashim
Dexter L. Lee
author_facet Justin L. Wilson
Rong Duan
Ahmed El-Marakby
Abdulmohsin Alhashim
Dexter L. Lee
author_sort Justin L. Wilson
collection DOAJ
description The anti-inflammatory properties of PPAR-α plays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-α agonist during a slow-pressor dose of Ang II (400 ng/kg/min). Ten to twelve week old male PPAR-α KO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-α KO mice compared to WT (161±4 mmHg versus 145±4 mmHg) and fenofibrate (145 mg/kg/day) reduced MAP in WT + Ang II mice (134±7 mmHg). Plasma IL-6 levels were higher in PPAR-α KO mice on day 12 of Ang II infusion (30±4 versus 8±2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treated WT mice (10±3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1, MCP-1 and COX-2 in WT + Ang II mice. Our results demonstrate that activation of PPAR-α attenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.
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spelling doaj-art-916dbd50a6cf43d88ead93dd6f2a2eea2025-08-20T02:10:03ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/645969645969Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused MiceJustin L. Wilson0Rong Duan1Ahmed El-Marakby2Abdulmohsin Alhashim3Dexter L. Lee4Department of Physiology and Biophysics, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, USADepartment of Physiology and Biophysics, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, USADepartment of Oral Biology and Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, GA 30912, USADepartment of Oral Biology and Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, GA 30912, USADepartment of Physiology and Biophysics, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, USAThe anti-inflammatory properties of PPAR-α plays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-α agonist during a slow-pressor dose of Ang II (400 ng/kg/min). Ten to twelve week old male PPAR-α KO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-α KO mice compared to WT (161±4 mmHg versus 145±4 mmHg) and fenofibrate (145 mg/kg/day) reduced MAP in WT + Ang II mice (134±7 mmHg). Plasma IL-6 levels were higher in PPAR-α KO mice on day 12 of Ang II infusion (30±4 versus 8±2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treated WT mice (10±3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1, MCP-1 and COX-2 in WT + Ang II mice. Our results demonstrate that activation of PPAR-α attenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.http://dx.doi.org/10.1155/2012/645969
spellingShingle Justin L. Wilson
Rong Duan
Ahmed El-Marakby
Abdulmohsin Alhashim
Dexter L. Lee
Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice
PPAR Research
title Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice
title_full Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice
title_fullStr Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice
title_full_unstemmed Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice
title_short Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice
title_sort peroxisome proliferator activated receptor α agonist slows the progression of hypertension attenuates plasma interleukin 6 levels and renal inflammatory markers in angiotensin ii infused mice
url http://dx.doi.org/10.1155/2012/645969
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