Endothelial NOD1 directs myeloid cell recruitment in atherosclerosis through VCAM‐1

What is it about?

Atherosclerosis, the underlying cause of myocardial infarction, stroke and peripheral vascular disease, is the major cause of morbidity and mortality in the developed world. It is a chronic disease characterized by vascular lipid retention and inflammation, and pattern recognition receptors (PRRs) are important contributors in early stages of the disease. Given the lack of proper biomarkers to define the onset of atherosclerosis, we felt compelled to identify an outstanding molecule participating in early arterial leukocyte recruitment without compromising immunity. Since the intracellular PRR NOD1 has been lately linked to cardiovascular diseases, we therefore hypothesized whether NOD1 might contribute to atherogenesis. In this paper we show that NOD1 expression is induced in atherosclerotic human and murine vessels. Nod1 inactivation in an atherosclerosis mouse model reduced not only atherosclerosis burden, but also monocyte and neutrophil accumulation in atheromata. Importantly, NOD1 regulated the expression of the endothelial adhesion molecule VCAM-1 in the early endothelial dysfunction. Sensing of either bacterial peptidoglycan or oxidized LDLs by endothelial NOD1, significantly enhanced firm adhesion of both sets of myeloid cells to the inflamed micro- and macro-vasculature in vivo. Therefore, our data define a major pro-atherogenic role for endothelial NOD1 in early leukocyte recruitment to the athero-prone vasculature. Thus, we introduce NOD1 as a potential prognostic molecule, as well as an innovative therapeutic target not only for coronary artery diseases, but also for other inflammatory diseases where the endothelium plays a key role.

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