S-EPMC7891542 - Overexpressed miR-335-5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome. - OmicsDI

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Dataset Information

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

ABSTRACT:

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-1?, TNF-?, 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-1?, TNF-?, 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.

SUBMITTER: Sun D

PROVIDER: S-EPMC7891542 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Sun Dingjun D Ma Tianyi T Zhang Yixue Y Zhang Fuwei F Cui Bo B

Journal of clinical laboratory analysis 20201205 2

<h4>Background</h4>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.<h4>Methods</h4>ACS-related gene microarray was collected from Gene Expression Omnibus database. After different agomir or antagomir, ...[more]

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Project description:Background and objectivesFormation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model.Subjects and methodsThirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-?, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor ?B (NF-?B) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-? stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively.ResultsTwo rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-? and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed that NF-?B and MMP expression was reduced in the MSC and SP groups compared to the VP group. Cell apoptosis decreased significantly in both the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein expression were higher in the plaques of the MSC group compared to the VP and SP groups.ConclusionsOur study results suggest that MSC transplantation can effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may potentially offer a new clinical application of MSC in atherosclerosis.