Page 14 - A. Aging

[A. Aging-8]

CD9 induces cellular senescence and aggravates

atherosclerotic plaque formation

Eok-Cheon Kim¹˙²˙#, Youlim Son¹˙²˙#, Jung Hee Cho¹˙²˙#, Da-Woon Lee¹˙², Yong Seop Park¹˙²,

Jun-Hyuk Choi³, Kyung-Hyun Cho⁴, Ki-Sun Kwon⁵, Jae-Ryong Kim¹˙²˙*

¹Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 42415,
Republic of Korea, ²Smart-aging Convergence Research Center, College of Medicine, Yeungnam University, Daegu

42415, Republic of Korea, ³Department of Pathology, College of Medicine, Yeungnam University, Daegu 42415,

Republic of Korea, ⁴School of Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea, ⁵Aging
Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea

CD9 is known to regulate cell adhesion and migration, cancer progression and metastasis, immune and allergic

responses, and viral infection. CD9 is upregulated in senescent endothelial cells, neointima hyperplasia, and
atherosclerotic plaques. However, its role in cellular senescence and atherosclerosis remains undefined. We

investigated the potential mechanism for CD9-mediated cellular senescence and its role in atherosclerotic plaque
formation. CD9 knockdown in senescent HUVECs significantly rescued senescence phenotypes, while CD9

upregulation in young cells accelerated senescence. CD9 regulated cellular senescence through a
phosphatidylinositide 3 kinase-AKT-mTOR-p53 signal pathway. CD9 expression increased in arterial tissues from

humans and rats with age, and in atherosclerotic plaques in humans and mice. Anti-mouse CD9 antibody noticeably
prevented the formation of atherosclerotic lesions in ApoE-/- mice and Ldlr-/- mice. Furthermore, CD9 ablation in

ApoE-/- mice decreased atherosclerotic lesions in aorta and aortic sinus. These results suggest that CD9 plays
critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that CD9
is a novel target for prevention and treatment of vascular aging and atherosclerosis.