Abstract

Abstract Atherosclerosis is a chronic inflammatory process that leads to plaque formation in large and medium size vessels. Th1 cells constitute a majority of plaque T cells and play a pro-atherogenic role. Signal transducer and activator of transcription 4 (Stat4) is a transcription factor involved in Th1 cell differentiation. To test a role of Stat4 in atherogenesis, we bred Stat4-deficient (Stat4-/-) and atherosclerosis-prone Apolipoprotein E (Apoe-/-) mice. Stat4 deficiency resulted in a 70% reduction in plaque burden in Stat4-/-Apoe-/- vs Apoe-/- mice (p<0.01). Surprisingly, reduced atherogenesis was not due to attenuated IFNγ production suggesting an IFNγ-independent pro-atherogenic role of Stat4. Stat4 is highly expressed in T cells, but also detected in macrophages (MΦ). To further test an impact of Stat4 deficiency in myeloid cells, we analyzed activation status of MΦ. Stat4-/-Apoe-/- CD11b+ MΦ expressed low levels of CD69, MHCII, and CD86 when pulsed with LPS vs Apoe-/- MΦ. Differentiated in vitro Stat4-/-Apoe-/- M1 or M2 MΦ also had reduced expression of CCL2 and CXCL10 vs Apoe-/- M1 and M2 MΦ. Importantly, the percentage of aortic Ly6C+ (p<0.02) and CD68+ (p<0.06) cells was reduced in Stat4-/-Apoe-/- vs Apoe-/- mice. The data provides evidence for a functional role of Stat4 in atherosclerosis by elevating levels of MΦ activation and aortic MΦ content, and thus promoting the localized aortic pro-inflammatory immune response. Supported by R01 HL112605 and Suppl.Grant 02S1.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.