![]() In fact, ApoE-deficient (ApoE −/−) mice are commonly used as a model of aortic atherosclerosis, sharing a greater degree of similarity to the development of atherosclerosis in humans compared to other models 9. APOE gene deficiency disrupts lipid transport into the liver, resulting in the development of hyperlipidemia and the progression of aortic atherosclerosis. Altogether, the intimal infiltration and modification of lipoproteins and their uptake mainly by macrophages, and consequent formation of lipid-filled foam cells, initiate atherosclerotic lesion formation 8.Īpolipoprotein E (ApoE), encoded by a gene with the same name ( APOE) located on chromosome 19 in humans, is involved in lipid transport and metabolism. In the intima, monocytes express scavenger receptors, phagocytose modified lipoproteins, and acquire the characteristics of pro-inflammatory macrophages, secreting various inflammatory cytokines, which, in turn, recruit T cells, and B cells 7. Monocyte recruitment from the bloodstream is probably the initial stage in the process of atherosclerotic plaque formation, activated by a regulated multistep process and mediated by chemoattractants and cell adhesion molecules such as vascular cell adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM) 6. These lipoproteins are then modified via different mechanisms, including oxidation by reactive oxygen species (ROS) 5. Therefore the endothelial cells become permeable to lipoproteins leading to the accumulation of low-density lipoproteins (LDLs) in the intima 4. This disturbed flow promotes the phosphorylation of occludin and weakens the tight junctions-mediated barrier function in endothelial cells 3. The blood flow in branches and curvatures is unevenly disturbed by the primary cilia of the endothelium 2. The atherosclerotic lesions are mainly found at the branches and curvatures of large blood vessels. Therefore, atherosclerosis can develop into ischemic disease, one of the world's leading causes of death 1. This induces an inflammatory reaction, and consequently, blood vessel wall fibrosis and luminal stenosis occur. Therefore, the induction and inhibition of HSPs should be considered for the prevention and treatment of atherosclerosis, respectively.Ītherosclerosis is caused by atheromas, mainly composed of lipid components lining blood vessel walls. Overall, these results indicate that HSPs exerts different effects in the context of aortic atherosclerosis, depending on its degree of progression. Of note, the induction of HSPs also promoted the formation of macrophage-derived foam cells. In fact, the short-term induction of HSPs, after the formation of atheromas, significantly increased the mRNA expression of tumor necrosis factor-alpha, and interleukin 6 in the aorta. ![]() In contrast, the induction of HSPs after the formation of atheromas promoted the progression of atherosclerosis. Remarkably, when HSPs were induced in apolipoprotein E deficient (ApoE −/−) mice prior to the formation of atheromas, the progression of atherosclerosis was inhibited the short-term induction of HSPs significantly decreased the mRNA expression of intercellular adhesion molecule 1 ( ICAM-1) and vascular cell adhesion molecule 1 ( VCAM-1) in the aorta. In this study, we induced the expression of HSPs and analyzed the effects on the development/progression of atherosclerosis in vivo. However, the relationship between HSPs and atherosclerosis remains unclear. The relationship between HSPs and various diseases has been extensively studied. Heat shock proteins (HSPs) are molecular chaperones that repair denatured proteins.
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