Your browser doesn't support javascript.
loading
LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis.
Li, Shu; He, Run-Chao; Wu, Shao-Guo; Song, Yu; Zhang, Ke-Lan; Tang, Mao-Lin; Bei, Yan-Rou; Zhang, Ting; Lu, Jin-Bo; Ma, Xin; Jiang, Min; Qin, Liang-Jun; Xu, Yudan; Dong, Xian-Hui; Wu, Jia; Dai, Xiaoyan; Hu, Yan-Wei.
Afiliação
  • Li S; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (S.L., R.-C.H., Y.S., K.-L.Z., M.-L.T., T.Z., M.J., X.-H.D., J.W., Y.-W.H.).
  • He RC; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (S.L., R.-C.H., Y.S., K.-L.Z., M.-L.T., T.Z., M.J., X.-H.D., J.W., Y.-W.H.).
  • Wu SG; Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital, Guangdong, China (S.-G.W.).
  • Song Y; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (S.L., R.-C.H., Y.S., K.-L.Z., M.-L.T., T.Z., M.J., X.-H.D., J.W., Y.-W.H.).
  • Zhang KL; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (S.L., R.-C.H., Y.S., K.-L.Z., M.-L.T., T.Z., M.J., X.-H.D., J.W., Y.-W.H.).
  • Tang ML; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (S.L., R.-C.H., Y.S., K.-L.Z., M.-L.T., T.Z., M.J., X.-H.D., J.W., Y.-W.H.).
  • Bei YR; Laboratory Medicine Center (Y.-R.B.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • Zhang T; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (S.L., R.-C.H., Y.S., K.-L.Z., M.-L.T., T.Z., M.J., X.-H.D., J.W., Y.-W.H.).
  • Lu JB; Department of Peripheral Vascular Surgery, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen (J.-B.L.).
  • Ma X; Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • Jiang M; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (S.L., R.-C.H., Y.S., K.-L.Z., M.-L.T., T.Z., M.J., X.-H.D., J.W., Y.-W.H.).
  • Qin LJ; Department of Pathology, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (L.J.Q.).
  • Xu Y; Laboratory Medicine Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China (Y.X.).
  • Dong XH; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (S.L., R.-C.H., Y.S., K.-L.Z., M.-L.T., T.Z., M.J., X.-H.D., J.W., Y.-W.H.).
  • Wu J; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangdong, China (S.L., R.-C.H., Y.S., K.-L.Z., M.-L.T., T.Z., M.J., X.-H.D., J.W., Y.-W.H.).
  • Dai X; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangdong, China (X.D.).
  • Hu YW; Clinical Research Institute, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hunan, China (X.D.).
Circ Res ; 134(1): 60-80, 2024 01 05.
Article em En | MEDLINE | ID: mdl-38084631
ABSTRACT

BACKGROUND:

Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis.

METHODS:

We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe-/-PSMB8-AS1KI) and global Apoe and proteasome subunit-ß type-9 (Psmb9) double knockout mice (Apoe-/-Psmb9-/-). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks.

RESULTS:

Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe-/-PSMB8-AS1KI mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe-/- mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe-/-PSMB8-AS1KI mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-ß type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe-/- mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout.

CONCLUSIONS:

PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aterosclerose / Placa Aterosclerótica / RNA Longo não Codificante Limite: Animals / Humans Idioma: En Revista: Circ Res Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aterosclerose / Placa Aterosclerótica / RNA Longo não Codificante Limite: Animals / Humans Idioma: En Revista: Circ Res Ano de publicação: 2024 Tipo de documento: Article