| First Author | Du M | Year | 2021 |
| Journal | FASEB J | Volume | 35 |
| Issue | 10 | Pages | e21951 |
| PubMed ID | 34551141 | Mgi Jnum | J:320398 |
| Mgi Id | MGI:6844885 | Doi | 10.1096/fj.202100947R |
| Citation | Du M, et al. (2021) Inhibition of NFAT suppresses foam cell formation and the development of diet-induced atherosclerosis. FASEB J 35(10):e21951 |
| abstractText | Deciphering the molecular and cellular processes involved in foam cell formation is critical for us to understand the pathogenesis of atherosclerosis. Nuclear factor of activated T cells (NFAT) is a transcription factor originally identified as a key player in the differentiation of T cells and maturation of immune system. Nowadays it has been brought into attention that NFAT also regulates multiple pathophysiological processes and targeted intervention in NFAT may be effective in the treatment of some cardiovascular diseases. However, whether NFAT is involved in foam cell formation remains elusive. NFAT in human monocyte-derived macrophage was activated by ox-LDL and translocated from the cytoplasm to the nucleus. NFAT then directly bound to peroxisome proliferator-activated receptor gamma (PPARgamma) in the nucleus and negatively regulated its transcriptional activity. NFATc2 knockdown or NFAT inhibitor 11R-VIVIT increased cholesterol efflux (by activating PPARgamma-LXRalpha-ABCA1 cascade) and reduced the uptake of modified lipoprotein (in a PPARgamma-independent way) in macrophage, thus prevented foam cell formation. Besides, 11R-VIVIT also exerted a protective role in the development of atherosclerosis in western diet-fed ApoE(-/-) mice. These results suggest NFAT inhibition as a potential therapeutic strategy in atherosclerosis. |
