STAT4 deficiency reduces the development of atherosclerosis in mice
dc.contributor.author | Taghavie-Moghadam, Parésa L. | |
dc.contributor.author | Gjurich, Breanne N. | |
dc.contributor.author | Jabeen, Rukhsana | |
dc.contributor.author | Krishnamurthy, Purna | |
dc.contributor.author | Kaplan, Mark H. | |
dc.contributor.author | Dobrian, Anca D. | |
dc.contributor.author | Nadler, Jerry L. | |
dc.contributor.author | Galkina, Elena V. | |
dc.contributor.department | Department of Pediatrics, IU School of Medicine | en_US |
dc.date.accessioned | 2017-07-25T20:22:11Z | |
dc.date.available | 2017-07-25T20:22:11Z | |
dc.date.issued | 2015-11 | |
dc.description.abstract | Atherosclerosis is a chronic inflammatory process that leads to plaque formation in large and medium sized vessels. T helper 1 (Th1) cells constitute the majority of plaque infiltrating pro-atherogenic T cells and are induced via IFNγ-dependent activation of T-box (Tbet) and/or IL-12-dependent activation of signal transducer and activator of transcription 4 (STAT4). We thus aimed to define a role for STAT4 in atherosclerosis. STAT4-deficiency resulted in a ∼71% reduction (p < 0.001) in plaque burden in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice fed chow diet and significantly attenuated atherosclerosis (∼31%, p < 0.01) in western diet fed Stat4(-/-)Apoe(-/-) mice. Surprisingly, reduced atherogenesis in Stat4(-/-)Apoe(-/-) mice was not due to attenuated IFNγ production in vivo by Th1 cells, suggesting an at least partially IFNγ-independent pro-atherogenic role of STAT4. STAT4 is expressed in T cells, but also detected in macrophages (MΦs). Stat4(-/-)Apoe(-/-)in vitro differentiated M1 or M2 MΦs had reduced cytokine production compare to Apoe(-/-) M1 and M2 MΦs that was accompanied by reduced induction of CD69, I-A(b), and CD86 in response to LPS stimulation. Stat4(-/-)Apoe(-/-) MΦs expressed attenuated levels of CCR2 and demonstrated reduced migration toward CCL2 in a transwell assay. Importantly, the percentage of aortic CD11b(+)F4/80(+)Ly6C(hi) MΦs was reduced in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice. Thus, this study identifies for the first time a pro-atherogenic role of STAT4 that is at least partially independent of Th1 cell-derived IFNγ, and primarily involving the modulation of MΦ responses. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Taghavie-Moghadam, P., Gjurich, B., Jabeen, R., Krishnamurthy, P., Kaplan, M. H., Dobrian, A. D., … Galkina, E. V. (2015). STAT4 Deficiency Reduces the Development of Atherosclerosis in mice. Atherosclerosis, 243(1), 169–178. http://doi.org/10.1016/j.atherosclerosis.2015.08.045 | en_US |
dc.identifier.issn | 1879-1484 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/13583 | |
dc.language.iso | en_US | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | 10.1016/j.atherosclerosis.2015.08.045 | en_US |
dc.relation.journal | Atherosclerosis | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Atherosclerosis | en_US |
dc.subject | genetics | en_US |
dc.subject | Interferon-gamma | en_US |
dc.subject | metabolism | en_US |
dc.subject | Macrophages | en_US |
dc.subject | cytology | en_US |
dc.subject | Plaque, Atherosclerotic | en_US |
dc.subject | STAT4 Transcription Factor | en_US |
dc.subject | Th1 Cells | en_US |
dc.title | STAT4 deficiency reduces the development of atherosclerosis in mice | en_US |
dc.type | Article | en_US |