Abstract
Anjali Roy
Abstract
Atherosclerosis, the cause of coronary artery disease, myocardial infraction, stroke, and peripheral artery disease, is an inflammatory disease. It involves the formation of lesions in the arteries that are characterized by inflammation, foam cell formation, cell death, and fibrosis. Macrophages, the major immune cell population in lesions, have been shown to play critical roles in all stages, including the initiation and progression of advanced atherosclerosis. The mechanisms that drive initial atherosclerotic lesion/ plaque building remain largely unknown. An increased understanding of the process of macrophage foam cell formation will help to develop novel therapeutic interventions for atherosclerosis. We studied the role of nitric oxide synthase 1 (NOS1) -derived nitric oxide (NO) on Oxidized low-density lipoprotein (OxLDL) uptake by bone marrow-derived macrophages (BMDMs). Pharmacological inhibition of NOS1 significantly reduces the OxLDL uptake by BMDMs. Also, the proinflammatory cytokine expression was significantly reduced in the presence of specific NOS1 inhibitors. One of the important observations revealed that OxLDL stimulation resulted in an increase of CD36 expression in macrophages, implying a feed-forward loop for foam cell formation. Further, we demonstrate that macrophage NOS1-derived NO has a role in endothelial junction permeability. Thus, this is a novel study involving NOS1 as critical players of foam cell formation and would reveal much about the critical molecular proteins involved in atherosclerosis. Therefore, targeting macrophage NOS1 and its regulated signaling proteins would be a useful strategy in reducing foam cell formation and dampening the atherosclerosis progression.