Overexpressed miR-335-5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome.
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.
['Sun|Dingjun|D|', 'Ma|Tianyi|T|', 'Zhang|Yixue|Y|', 'Zhang|Fuwei|F|', 'Cui|Bo|B|https://orcid.org/0000-0002-2552-9344']
D020413:3' Untranslated Regions D054058:Acute Coronary Syndrome D000818:Animals D000070416:Antagomirs D003094:Collagen D003959:Diamines D015870:Gene Expression D006801:Humans D000072100:Jagged-1 Protein D008055:Lipids D008297:Male D008810:Mice, Inbred C57BL D035683:MicroRNAs D058226:Plaque, Atherosclerotic D051880:Receptors, Notch D013844:Thiazoles
atherosclerotic vulnerable plaque acute coronary syndrome revascularization notch signaling JAG1 innate immune response of macrophage microRNA-335-5p