Abstract
Background and Aims: Acute coronary syndrome (ACS) is a group of clinical syndromes characterized by rupture or erosion of atherosclerotic unstable plaques. Effective intervention for vulnerable plaques (VP) is of great significance to reduce adverse cardiovascular events.Methods: Fbn1C1039G+/− mice were crossbred with LDLR−/− mice to obtain a novel model for atherosclerotic VP. After the mice were fed with a high-fat diet (HFD) for 12 or 24 weeks, pathological staining and immunohistochemistry analyses were employed to evaluate atherosclerotic lesions.Results: Compared to control mice, Fbn1C1039G+/−LDLR−/− mice developed more severe atherosclerotic lesions, and the positive area of oil red O staining in the aortic sinus was significantly increased after 12 weeks (21.7 ± 2.0 vs. 6.3 ± 2.1) and 24 weeks (32.6 ± 2.5 vs. 18.7 ± 2.6) on a HFD. Additional vulnerable plaque characteristics, including significantly larger necrotic cores (280 ± 19 vs. 105 ± 7), thinner fiber caps (14.0 ± 2.8 vs. 32.6 ± 2.7), apparent elastin fiber fragmentation and vessel dilation (3,010 ± 67 vs. 1,465 ± 49), a 2-fold increase in macrophage number (8.5 ± 1.0 vs. 5.0 ± 0.6), obviously decreased smooth muscle cell number (0.6 ± 0.1 vs. 2.1 ± 0.2) and an ~25% decrease in total collagen content (33.6 ± 0.3 vs. 44.9 ± 9.1) were observed in Fbn1C1039G+/−LDLR−/− mice compared with control mice after 24 weeks. Furthermore, spontaneous plaque rupture, neovascularization, and intraplaque hemorrhage were detected in the model mouse plaque regions but not in those of the control mice.Conclusions: Plaques in Fbn1C1039G+/−LDLR−/− mice fed a HFD show many features of human advanced atherosclerotic unstable plaques. These results suggest that the Fbn1C1039G+/−LDLR−/− mouse is a novel model for investigating the pathological and physiological mechanisms of advanced atherosclerotic unstable plaques.
Highlights
Atherosclerosis (AS), which results from the accumulation of lipid-rich plaques within artery walls, has become one of the biggest risks to human health
To determine the effect of the mutation of the fibrillin-1 gene in LDLR−/− mice, we crossbred LDLR−/− mice with of LDLR−/− mice after 12 and 24 weeks of high-fat diet (HFD) (Figure 3A). This phenomenon was observed in plaques in the fulllength aortas of Fbn1C1039G+/−LDLR−/− mice compared with LDLR−/− mice (Figure 3B)
B, the genotype was identified by polymerase chain reaction, gene sequencing analysis, and agarose gel electrophoresis. Since it is difficult for LDLR−/− mice to develop atherosclerosis by feeding on a chow diet only, we administered a HFD to the two groups of mice
Summary
Atherosclerosis (AS), which results from the accumulation of lipid-rich plaques within artery walls, has become one of the biggest risks to human health. Studies have demonstrated that the growth of atherosclerotic plaques has obvious stages [1]. With the continuous progression of plaques and exacerbation of the inflammatory response, a large number of growth factors and inflammatory mediators are secreted by macrophages and other cells, and lipid streaks gradually emerge [3]. As smooth muscle cells (SMCs) proliferate and migrate to intimal tissue, more elastin and collagen are produced, and lipid streaks gradually change into fibrous plaques. Vulnerable plaques are characterized by a large necrotic core and a thinner fibrous cap and have a high risk of sudden rupture and thrombosis leading to acute coronary events [5]. Acute coronary syndrome (ACS) is a group of clinical syndromes characterized by rupture or erosion of atherosclerotic unstable plaques. Effective intervention for vulnerable plaques (VP) is of great significance to reduce adverse cardiovascular events
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