High-density lipoproteins induce miR-223-3p biogenesis and export from myeloid cells: Role of scavenger receptor BI-mediated lipid transfer.
Atherosclerosis
; 286: 20-29, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31096070
ABSTRACT
BACKGROUND AND AIMS:
We recently showed that miR-223-3p on high-density lipoproteins (HDL) is exported to endothelial cells, where it inhibits inflammation. However, the origin of miR-223-3p on HDL is unknown. We hypothesize that HDL-associated miR-223-3p originates in myeloid cells and is exported to HDL in a scavenger receptor BI (SR-BI)-dependent manner.METHODS:
Polymorphonuclear neutrophils (PMNs) and human monocyte derived macrophages (HMDMs) were incubated with native HDL (nHDL) or discoidal reconstituted HDL (rHDL). Total RNA was isolated before and after incubation. Mature and primary miR-223-3p (pri-mir-223-3p) levels were quantified by real-time PCR.RESULTS:
Incubation with nHDL and rHDL increased miR-223-3p export from PMNs and HMDMs. In PMNs, nHDL but not rHDL, increased mature and pri-mir-223-3p. Incubation with HDL also increased Dicer mRNA, a critical regulator of miRNA biogenesis. Incubation of HMDMs with nHDL did not increase cellular levels of mature miR-223-3p, but significantly increased pri-mir-223 levels. Incubation with rHDL had no effect on either mature or pri-mir-223-3p levels. Activated PMNs increased miR-223-3p export to HDL and the production of reactive oxygen species and activated protein kinase C. Blocking HDL binding to SR-BI increased miR-223-3p export to HDL in both PMNs and HMDMs, but did not affect mature and primary miR-223-3p levels. Chemical inhibition of cholesterol flux by Block Lipid Transport (BLT)-1 inhibited HDL-induced pri-mir-223 expression in PMNs.CONCLUSIONS:
HDL-associated miR-223-3p originates in PMNs and macrophages. HDL stimulates miR-223-3p biogenesis in PMNs in a process that is regulated by SR-BI-mediated lipid flux.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Mieloides
/
MicroRNAs
/
Receptores Depuradores Classe B
/
Lipoproteínas HDL
Limite:
Humans
Idioma:
En
Revista:
Atherosclerosis
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Austrália