Overexpressed miR-335-5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome

• Main Authors: Cui, B. (Author), Ma, T. (Author), Sun, D. (Author), Zhang, F. (Author), Zhang, Y. (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: 24-diamino-5-phenylthiazole; 3' untranslated region; 3' Untranslated Regions; acute coronary syndrome; Acute Coronary Syndrome; animal; animal cell; animal experiment; animal model; animal tissue; Animals; antagomir; Antagomirs; Article; atherosclerotic plaque; atherosclerotic vulnerable plaque; blood; C57BL mouse; collagen; Collagen; collagen fiber; controlled study; coronary artery atherosclerosis; diamine; Diamines; enzyme linked immunosorbent assay; gene expression; Gene Expression; gene function; gene overexpression; genetic database; genetic regulation; genetics; heart muscle revascularization; human; human cell; Humans; innate immune response of macrophage; innate immunity; intercellular adhesion molecule 1; interleukin 1beta; interleukin 6; JAG1; JAG1 protein, human; Jagged-1 Protein; lipid; lipid storage; Lipids; macrophage function; male; Male; matrix metalloproteinase; metabolism; Mice, Inbred C57BL; microarray analysis; microRNA; microRNA 335 5p; microRNA-335-5p; MicroRNAs; MIRN335 microRNA, human; Mirn335 microRNA, mouse; monocyte chemotactic protein 1; mouse; nonhuman; Notch receptor; notch signaling; Notch signaling; pathophysiology; Plaque, Atherosclerotic; protein expression; protein Jagged 1; protein targeting; real time reverse transcription polymerase chain reaction; Receptors, Notch; revascularization; RNA analysis; RNA interference; thiazole derivative; Thiazoles; tissue inhibitor of metalloproteinase 1; tissue inhibitor of metalloproteinase 2; tumor necrosis factor; unclassified drug; vascular cell adhesion molecule 1; Western blotting
• Online Access: View Fulltext in Publisher
• ISBN: 08878013 (ISSN)
• DOI: 10.1002/jcla.23608

Background: Acute coronary syndrome (ACS) may induce cardiovascular death. The correlation of mast cells related microRNAs (miRs) with risk of ACS has been investigated. We explored regulatory mechanism of miR-335-5p on macrophage innate immune response, atherosclerotic vulnerable plaque formation, and revascularization in ACS in relation to Notch signaling. Methods: ACS-related gene microarray was collected from Gene Expression Omnibus database. After different agomir or antagomir, or inhibitor of Notch signaling treatment, IL-6, IL-1β, TNF-α, MCP-1, ICAM-1, and VCAM-1 levels were tested in ACS mice. Additionally, Notch signaling-related genes and matrix metalloproteinases (MMPs) were measured after miR-335-5p interference. Finally, mouse atherosclerosis, lipid accumulation, and the collagen/vessel area ratio of plaque were determined. Results: miR-335-5p targeted JAG1 and mediated Notch signaling in ACS. miR-335-5p up-regulation and Notch signaling inhibition reduced expression of JAG1, Notch pathway-related genes, IL-6, IL-1β, TNF-α, MCP-1, ICAM-1, VCAM-1, and MMPs, but promote TIMP1 and TIMP2 expression. Additionally, vulnerable plaques were decreased and collagen fiber contents were observed to increase after miR-335-5p overexpression and Notch signaling inhibition. Conclusions: Overexpression of miR-335-5p inhibited innate immune response of macrophage, reduced atherosclerotic vulnerable plaque formation, and promoted revascularization in ACS mice targeting JAG1 through Notch signaling. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC