The Specific Role of CCL8 Chemokine in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease that represents the primary cause of heart disease and stroke. C-C motif chemokine ligand 8 (CCL8) has been found in many diseases’ pathogenesis. Nevertheless, its molecular mechanism in atherosclerosis (AS) remains to be elucidated. Human microvascular endothelial cells (HMEcs) were stimulated by IFNα, IFNγand LPS, to establish experimental atherosclerosis. Recruitment of blood leukocytes to the injured vascular endothelium characterizes the initiation and progression of atherosclerosis and involves many inflammatory mediators, modulated by cells of both innate and adaptive immunity. The pro-inflammatory cytokine, interferon (IFN)-γ derived from T cells, is vital for both innate and adaptive immunity and is also expressed at high levels in atherosclerotic lesions. As such, IFN-γ plays a crucial role in the pathology of atherosclerosis through activation of signal transducer and activator of transcription (STAT)1. Our study indeed provides evidence that in HMECs STAT1 coordinates a platform for cross-talk between IFNγ and TLR4, and identifies a STAT1-dependent gene signature that reflects a pro-atherogenic state in coronary artery disease (CAD) and carotid atherosclerosis. Taken together, our data indicate that in the presence of appropriate stimuli, HMECs are highly responsive and consistently express CCL8. However, upregulation of CCL8 led to suggest CCL8 could be an atherosclerosis therapeutic target. HMECs may therefore provide a better model for in vitro studies of atherosclerosis.

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