Role of perivascular adipose tissue in nicotine-induced endothelial cell inflammatory responses

Smoking is considered to be one of the primary causes of atherosclerosis and vascular injury. Previous studies have shown that nicotine in tobacco can lead to vascular inflammation and endothelial dysfunction. Perivascular adipose tissue (PVAT) is known to secrete various types of adipokines to maintain vascular homeostasis. The present study investigated whether nicotine-induced PVAT malfunction can accelerate endothelial inflammation and eventually lead to endothelial dysfunction. The levels of inflammatory adipokines, including nuclear factor (NF)-kappa B, interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha, the ICAM-1 and VCAM-1 adhesion molecules and secretion of adiponectin were assessed in mature-adipocytes and endothelial cells cultured alone or in co-culture under nicotine stimulation. It was found that nicotine reduced the secretion of adiponectin and stimulated secretion of the NF-kappa B, IL-1 beta, IL-6 and TNF-alpha inflammatory adipokines in mature adipocytes. Although nicotine stimulated endothelial cells to secrete IL-1 beta and IL-6, no significant increase in the secretion of TNF-alpha was observed. The co-culture of mature adipocytes with endothelial cells markedly augmented the expression of the NF-kappa B, IL-1 beta, IL-6 and TNF-alpha inflammatory adipokines and the ICAM-1 and VCAM-1 adhesion molecules, and significantly lowered the levels of adiponectin. These findings suggested that nicotine induced mature adipocyte dysfunction, which caused the abnormal secretion of adiponectin and inflammatory adipokines, and exacerbated endothelial inflammation. These findings also suggested a mechanism whereby nicotine induced the secretion of adiponectin and inflammatory cytokines by adipocytes. The results of the present study elucidated a novel pathway induced by cigarette smoke, which contributed to atherosclerosis and vascular injury.