| First Author | Taghavie-Moghadam PL | Year | 2015 |
| Journal | Atherosclerosis | Volume | 243 |
| Issue | 1 | Pages | 169-78 |
| PubMed ID | 26386214 | Mgi Jnum | J:331035 |
| Mgi Id | MGI:6871249 | Doi | 10.1016/j.atherosclerosis.2015.08.045 |
| Citation | Taghavie-Moghadam PL, et al. (2015) STAT4 deficiency reduces the development of atherosclerosis in mice. Atherosclerosis 243(1):169-78 |
| abstractText | 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 IFNgamma-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 approximately 71% reduction (p < 0.001) in plaque burden in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice fed chow diet and significantly attenuated atherosclerosis ( approximately 31%, p < 0.01) in western diet fed Stat4(-/-)Apoe(-/-) mice. Surprisingly, reduced atherogenesis in Stat4(-/-)Apoe(-/-) mice was not due to attenuated IFNgamma production in vivo by Th1 cells, suggesting an at least partially IFNgamma-independent pro-atherogenic role of STAT4. STAT4 is expressed in T cells, but also detected in macrophages (MPhis). Stat4(-/-)Apoe(-/-)in vitro differentiated M1 or M2 MPhis had reduced cytokine production compare to Apoe(-/-) M1 and M2 MPhis that was accompanied by reduced induction of CD69, I-A(b), and CD86 in response to LPS stimulation. Stat4(-/-)Apoe(-/-) MPhis 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) MPhis 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 IFNgamma, and primarily involving the modulation of MPhi responses. |
