title: Endothelial enriched microRNAs regulate angiotensin II-induced endothelial inflammation and migration.
abstract: Inflammation is observed at all stages of atherosclerosis. The initial stage of atherosclerosis is characterized by recruitment of leukocytes to activated endothelial cells (ECs). MicroRNAs (miRNAs) are a class of 19-25 nucleotides, non-protein-coding RNAs that repress target gene expression by translational inhibition or mRNA degradation. The link between miRNA and endothelial functions is largely unknown. Northern blot showed that miR-155 and miR-221 were highly expressed in human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs). Bioinformatics analysis proposed Ets-1, a key endothelial transcription factor for inflammation and tube formation, as a candidate target for miR-155 and miR-221/222 cluster. The effect was demonstrated by luciferase reporter assay and Western blot. By using Western blot, we also confirmed that angiotensin II type 1 receptor (AT1R) is a target of miR-155 in HUVECs. Quantitative PCR showed that Ets-1 and its downstream genes, including VCAM1, MCP1 and FLT1, were upregulated in angiotensin II-stimulated HUVECs, and this effect was partially reversed by overexpression of miR-155 and miR-221/222. In addition, cell adhesion assay revealed overexpression of miR-155 and miR-221/222 effectively decreased the adhesion of Jurkat T cells to Ang II-stimulated HUVECs. Besides, by targeting AT1R, miR-155 can also decrease the HUVECs migration in response to Ang II. In summary, HUVECs highly expressed miR-155 may co-target AT1R and Ets-1 while miR-221/222 targets Ets-1, which indirectly regulate the expression of several inflammatory molecules of ECs, and therefore attenuate the adhesion of Jurkat T cells to activated HUVECs and reduce HUVECs migration. These findings present possible therapeutic targets in atherosclerosis.
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, PR China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zhu
authors.forename: Dongze
authors.initials: D
authors.lastname: Zhang
authors.forename: Sifeng
authors.initials: S
authors.lastname: Chen
authors.forename: Xuemei
authors.initials: X
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Xinmiao
authors.initials: X
authors.lastname: Huang
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Guo
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yuan
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Qin
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D050197:Atherosclerosis / Q000503:physiopathology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology; D019169:Jurkat Cells; D035683:MicroRNAs / Q000502:physiology*; D050784:Proto-Oncogene Protein c-ets-1 / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism
chemical_list: D000804:Angiotensin II; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1; D044140:Receptor, Angiotensin, Type 1; C494041:ETS1 protein, human; C524942:MIRN155 microRNA, human; C525709:MIR221, human