Atherosclerosis is a progressive vascular wall inflammatory disease, and the
rupture of atherosclerotic vulnerable plaques is the leading cause of morbidity and mortality worldwide. This study intended to explore the potential mechanisms behind plaque
rupture and
thrombosis in ApoE knockout mice. The spontaneous plaque
rupture models were established, and left carotid artery tissues at different time points (1-, 2-, 4-, 6-, 8-, 12-, and 16-week post-surgery) were collected. By the extent of plaque
rupture, plaque was defined as (1) control groups, (2)
atherosclerotic plaque group, and (3) plaque
rupture group. Macrophage (CD68), MMP-8, and MMP-13 activities were measured by immunofluorescence.
Cytokines and inflammatory markers were measured by ELISA. The left carotid artery sample tissue was collected to evaluate the
miRNAs expression level by
miRNA-microarray. Bioinformatic analyses were conducted at three levels: (2) vs. (1), (3) vs. (2), and again in seven time series analysis. The plaque
rupture with
thrombus and intraplaque
hemorrhage results peaked at 8 weeks and decreased thereafter. Similar trends were seen in the number of plaque macrophages and
lipids, the expression of
matrix metalloproteinase, and the atherosclerotic and plasma
cytokine levels.
MiRNA-microarray showed that miR-322-5p and miR-206-3p were specifically upregulated in the
atherosclerotic plaque group compared with those in the control group. Meanwhile, miR-466h-5p was specifically upregulated in the plaque
rupture group compared with the
atherosclerotic plaque group. The highest incidence of plaque
rupture and
thrombosis occurred at 8 weeks post-surgery. miR-322-5p and miR-206-3p may be associated with the formation of
atherosclerotic plaques. miR-466h-5p may promote
atherosclerotic plaque rupture via apoptosis-related pathways.