Open AccessOverexpressed miR‐335‐5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome
Author(s) -
Sun Dingjun,
Ma Tianyi,
Zhang Yixue,
Zhang Fuwei,
Cui Bo
Publication year - 2021
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.23608
Subject(s) - notch signaling pathway , jag1 , signal transduction , matrix metalloproteinase , microrna , innate immune system , cancer research , medicine , microbiology and biotechnology , immunology , biology , immune system , gene , biochemistry
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.