Molecular Genetic Analysis Of C-X-C Motif Chemokine Ligand 9 (CXCL9) As A Novel Biomarker In Atherosclerosis
Keywords:
Abstract
For almost a century, many have considered lipids as the sine qua non of atherosclerosis. However, in 1856 Rudolf Virchow introduced a theory that inflammation is the driving force of atherogenesis. 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 STAT1.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 Cxcl9. HMECs may therefore provide a better model for in vitro studies of atherosclerosis.
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