Abstract
Atherosclerosis is the pathological basis of coronary artery disease (CAD) and causes high mortality. Thus, early detection is thought to be crucial in reducing the risk of CAD. Uncovering the mechanisms of the progression and regression of atherosclerosis will provide insights into discovering novel biomarkers to identify subjects at risk for CAD and improve prevention. We established atherosclerosis progression and regression in a rabbit model. Then, we extracted mRNA of the abdominal aorta from control, model and recovery groups to perform gene chip analysis. Candidate biomarkers were screened by large-scale gene analysis and validated in patients with CAD or with CAD recovery by ELISA. The differentially expressed genes in the progression and regression of atherosclerosis were mainly enriched in four clusters. Genes associated with inflammation and extracellular matrix were returned to normal or close-to-normal levels much earlier than genes associated with metabolism and sarcoplasmic proliferation, and they were maintained downregulated or upregulated after feeding a normal diet. We then selected four candidate biomarkers and found that lipoprotein lipase (LPL), bone morphogenetic protein 7 and somatostatin concentrations could indicate CAD diagnosis. In addition, LPL and macrophage cationic peptide 2 can be indicators of the prognosis of CAD. Molecular changes during the progression and regression of atherosclerosis in rabbits were revealed, and candidate regulators were identified. The identified factors could be used as novel biomarkers and targets for improving the diagnosis and prognosis of human CAD in the future.
Highlights
Atherosclerosis is the pathological basis of coronary artery disease (CAD), threatening human health and leading to high mortality
To investigate the gene expression pattern in the progression and regression of atherosclerosis, we established a rabbit model of atherosclerosis by feeding rabbits a high-cholesterol diet and including balloon injury, followed by feeding a caloric restriction diet. We found that both serum total cholesterol (TCH) and low-density lipoprotein cholesterol (LDL-c) concentrations were significantly increased during the high-cholesterol diet period (AS30) compared with the control ( p, 0.05)
We established a rabbit model of progression and regression of atherosclerosis through balloon injury followed by feeding a high-cholesterol diet or a caloric restriction diet
Summary
Atherosclerosis is the pathological basis of coronary artery disease (CAD), threatening human health and leading to high mortality. Despite percutaneous coronary intervention (PCI) being a well established and useful technique for CAD, various other factors such as inflammation and insulin resistance can lead to restenosis and threaten survival [1,2]. Early detection and control of risk factors is thought to be crucial in reducing the risk of CAD. Uncovering additional mechanisms of the progression and regression of atherosclerosis will provide insights into discovering novel biomarkers to identify subjects at risk for CAD and enable the administration of interventional approaches. Establishing an appropriate experimental animal model is essential for studying the pathophysiology of atherosclerosis. Animal models should reflect the most important aspects of lipid metabolism and the features of lesions, such
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