| First Author | Kriska T | Year | 2014 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 306 |
| Issue | 1 | Pages | H26-32 |
| PubMed ID | 24163073 | Mgi Jnum | J:207723 |
| Mgi Id | MGI:5559420 | Doi | 10.1152/ajpheart.00287.2013 |
| Citation | Kriska T, et al. (2014) Role of macrophage PPARgamma in experimental hypertension. Am J Physiol Heart Circ Physiol 306(1):H26-32 |
| abstractText | Targeted disruption of the Alox15 gene makes mice resistant to angiotensin II-, DOCA/salt-, and N(omega)-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)gamma agonists, we hypothesized that activation of macrophage PPARgamma is the key step in Alox15 mediation of hypertension. Thioglycollate, used for macrophage elicitation, selectively upregulated PPARgamma 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 PPARgamma was further specified by using the selective PPARgamma antagonist GW9662. WT mice treated with 50 mug/kg daily dose of GW9662 for 12 days became resistant to L-NAME-induced hypertension. The PPARgamma antagonist treatment also prevented L-NAME-induced hypertension in thioglycollate-injected Alox15(-/-) mice, indicating a PPARgamma-mediated effect in macrophage elicitation and the resultant hypertension. These results indicate a regulatory role for macrophage-localized PPARgamma in L-NAME-induced experimental hypertension. |
