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

Abstract

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)‑κB, interleukin (IL)‑1β, IL‑6 and tumor necrosis factor (TNF)‑α, 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‑κB, IL‑1β, IL‑6 and TNF‑α inflammatory adipokines in mature adipocytes. Although nicotine stimulated endothelial cells to secrete IL‑1β and IL‑6, no significant increase in the secretion of TNF‑α was observed. The co‑culture of mature adipocytes with endothelial cells markedly augmented the expression of the NF‑κB, IL‑1β, IL‑6 and TNF‑α 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.

Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis

“…Endothelial cells play a critical role in maintaining the integrity of vessel wall, and endothelial cell injury is an initiator of atherosclerosis 28 and has been documented in cigarette smokers 28 . Moreover, nicotine has also been shown to participate in vascular inflammation and endothelial dysfunction 29 , 30 .…”

Quit smoking to outsmart atherogenesis: Molecular mechanisms underlying clinical evidence

“…The up-regulation of inflammatory genes, including Interleukin-1 and COX-2, after smoke exposure, has been demonstrated in ApoE −/− mice, with proatherogenic effects [11]. Furthermore, nicotine has been shown to trigger the secretion of pro-inflammatory adipokines from the perivascular adipose tissue [12]. Mounting evidence supports the view of a chronic inflammatory state that is common in smokers, characterized by depression of suppressor T-cell function.…”

Exosomes derived from mangiferin‑stimulated perivascular adipose tissue ameliorate endothelial dysfunction

“…It is well established that adipose tissue inflammation-induced cardiovascular diseases are associated with diabetes and obesity. In particular, PVAT dysfunction serves a vital role in endothelial injury, which may result in vascular damage (24). Additionally, the anatomical and functional features of PVAT d etermine its vital role in the regulation of endothelial homeostasis (25).…”