Abstract
Here, we investigated the effect of chronic mild stress (CMS) on the development of atherosclerosis as well as the expression of Toll-like receptors (TLRs) signaling pathway in adolescent apolipoprotein E knockout (apoE-/-) mice. Mice were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein E knockout mice subjected to CMS, we compared gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87 genes. We found that atherosclerosis lesions both in aortic tress and sinuses of CMS mice were significantly increased linearly in response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88 (MyD88), and IL-1β, and 28 genes were downregulated compared with nonstressed mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were associated with significant increases in levels of expression of TLR4, MyD88, nuclear factor κB (NF-κB), MCP-1, IL-1β, TNF-α, and sICAM-1. Taken together, our results suggest an important role for TLR4 signaling pathway in atherosclerosis in a CMS mouse model.
Highlights
Conventional cardiovascular risk factors such as high blood pressure and high cholesterol do not account fully for variation in coronary heart disease, suggesting additional risk factors warrant investigation
In the present study, we found that chronic mild stress (CMS) mice showed a significant increase in gene expression of TLR4 pathway compared with age-matched control mice
Concomitant with lesion progression in CMS apoE-/- mice, we demonstrated a markedly increased in the expression of TLR4, myeloid differentiation factor 88 (MyD88), and NF-kB mRNA in the arterial lesions of these mice
Summary
Conventional cardiovascular risk factors such as high blood pressure and high cholesterol do not account fully for variation in coronary heart disease, suggesting additional risk factors warrant investigation. A considerable amount of evidence has shown that psychosocial factors play an important role in the etiology and progression of certain cardiovascular diseases such as atherosclerosis [1, 2]. Despite accumulating evidence and increased awareness of the importance of stress in the pathogenesis of atherosclerosis, the underlying mechanisms are still largely unknown [4]. Accumulating evidence indicates that atherosclerosis is the result of a prolonged and excessive inflammatory process in the vascular wall [6]. It is, important to inquire whether stressful psychosocial factors can initiate or participate in the inflammatory events that culminate in atherosclerosis. To investigate whether TLRs might be involved in the effect of CMS, we compare gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87genes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
