A novel model of myocardial infarction based on atherosclerosis in mice.

RATIONALE: Coronary artery ligation to induce myocardial infarction (MI) and ischemia injury in mice is typically performed in normal mice, but This is not consistent with disease progression. There should be atherosclerosis (AS) first, followed by MI. OBJECTIVE: We tried a novel model to induce MI that was established on atherosclerosis in mice. This approach was much more consistent with disease progression. METHODS: In this study, Mice lacking apolipoprotein E (ApoE-/-) were randomly divided into four groups. The mice of the control and MI groups were fed normal diet for 24-weeks, while the mice of AS and AS + MI groups were fed high-fat diet (HFD). After 23 weeks, the mice of MI and AS + MI groups were ligated with coronary arteries. A week later, after echocardiography, analysis of plaque and myocardium were conducted on aortic and heart, then the serum, aorta and heart tissues were further detected. RESULTS: Our results showed that AS model mice exhibited significant body weight gain, dyslipidemia and atherosclerotic lesions formation which were in accordance with the pathological changes of AS. Co-treatment with AS and MI led to higher operative mortality and heart pathological were in accordance with the pathological changes of MI. In addition, Echocardiography and NT pro-BNP revealed co-treatment with AS and MI led to deterioration of cardiac function. AS also aggravated myocardial inflammatory cell infiltration and fibrosis post-MI. CONCLUSIONS: Together, it is feasible to establish myocardial infarction model based on atherosclerosis model.

Silencing of junctional adhesion molecule-like protein attenuates atherogenesis and enhances plaque stability in ApoE-/- mice.

Background: Although junctional adhesion molecule-like protein (JAML) has recently been implicated in leukocyte recruitment during inflammation and wound repair, its role in atherosclerosis remains to be elucidated. Methods and results: First, we showed that JAML was strongly expressed in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with atherosclerotic plaques of ApoE-/- mice. Co-immunofluorescence staining showed that JAML was mainly expressed in macrophages. Enhanced expression of JAML in cultured macrophages was observed following exposure of the cells to oxLDL. The functional role of JAML in atherosclerosis and macrophages function was assessed by interference of JAML with shRNA in vivo and siRNA in vitro Silencing of JAML in mice significantly attenuated atherosclerotic lesion formation, reduced necrotic core area, increased plaque fibrous cap thickness, decreased macrophages content and inflammation. In addition, histological staining showed that JAML deficiency promoted plaques to stable phenotype. In vitro, JAML siRNA treatment lowered the expression of inflammatory cytokines in macrophages treated with oxLDL. The mechanism by which JAML mediated the inflammatory responses may be related to the ERK/NF-κB activation. Conclusions: Our results demonstrated that therapeutic drugs which antagonize the function of JAML may be a potentially effective approach to attenuate atherogenesis and enhance plaque stability.