Role of macrophage PPARγ in experimental hypertension. Am J Physiol Heart Circ Physiol 2014 Jan 01;306(1):H26-32
Date
10/29/2013Pubmed ID
24163073Pubmed Central ID
PMC3920151DOI
10.1152/ajpheart.00287.2013Scopus ID
2-s2.0-84891514189 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Targeted disruption of the Alox15 gene makes mice resistant to angiotensin II-, DOCA/salt-, and N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced experimental hypertension. Macrophages, a primary source of Alox15, are facilitating this resistance, but the underlying mechanism is not known. Because Alox15 metabolites are peroxisome proliferator-activated receptor (PPAR)γ agonists, we hypothesized that activation of macrophage PPARγ is the key step in Alox15 mediation of hypertension. Thioglycollate, used for macrophage elicitation, selectively upregulated PPARγ and its target gene CD36 in peritoneal macrophages of both wild-type (WT) and Alox15(-/-) mice. Moreover, thioglycollate-injected Alox15(-/-) mice became hypertensive upon L-NAME treatment. A similar hypertensive effect was observed with adoptive transfer of thioglycollate-elicited Alox15(-/-) macrophages into Alox15(-/-) recipient mice. The role of PPARγ was further specified by using the selective PPARγ antagonist GW9662. WT mice treated with 50 μg/kg daily dose of GW9662 for 12 days became resistant to L-NAME-induced hypertension. The PPARγ antagonist treatment also prevented L-NAME-induced hypertension in thioglycollate-injected Alox15(-/-) mice, indicating a PPARγ-mediated effect in macrophage elicitation and the resultant hypertension. These results indicate a regulatory role for macrophage-localized PPARγ in L-NAME-induced experimental hypertension.
Author List
Kriska T, Cepura C, Gauthier KM, Campbell WBAuthors
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinTamas Kriska PhD Research Scientist I in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnilidesAnimals
Arachidonate 12-Lipoxygenase
Arachidonate 15-Lipoxygenase
CD36 Antigens
Hypertension
Macrophages
Mice
Mice, Inbred C57BL
NG-Nitroarginine Methyl Ester
PPAR gamma
Thioglycolates
Up-Regulation