An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.
Jun-Ichi AbeMasaki ImanishiShengyu LiAijun ZhangKyung Ae KoVenkata S K SamanthapudiLing-Ling LeeAngelica Paniagua BojorgesYoung Jin GiBrian P HobbsAnita DeswalJoerg HerrmannSteven H LinEduardo N ChiniYing H ShenKeri L SchadlerThi-Hong-Minh NguyenAnisha A GupteCielito C Reyes-GibbySai-Ching J YeungRei J AbeElizabeth A Olmsted-DavisSunil KrishnanRobert DantzerNicolas L PalaskasJohn P CookeHenry J PownallMomoko YoshimotoKeigi FujiwaraDale J HamiltonJared K BurksGuangyu WangNhat-Tu LeSivareddy KotlaPublished in: Circulation research (2023)
We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation.
Keyphrases
- cell cycle arrest
- endothelial cells
- dna damage
- pi k akt
- stem cells
- stress induced
- cell death
- signaling pathway
- epithelial mesenchymal transition
- high glucose
- oxidative stress
- cardiovascular disease
- cell proliferation
- induced apoptosis
- acute myeloid leukemia
- coronary artery disease
- type diabetes
- bone marrow
- cancer stem cells