Obesity associated inflammatory perivascular adipose tissue promotes endothelial inflammation and atherosclerosis in mice

Atherosclerosis (AS) is one of the leading causes of death worldwide. AS is a state of chronic, low-grade inflammation and is closely associated with obesity. The aim of this study was therefore to investigate the role of obesity-related inflammatory perivascular adipose tissue (PVAT) in the progression of AS, independently of hyperlipidaemia. First, mice were fed either a normal diet (ND) or a high-fat diet (HFD) for 16 weeks. Subsequently, PVAT surrounding the abdominal aorta was collected. Having confirmed that obesity exacerbates the inflammatory characteristics of PVAT, PVAT from the ND or HFD group was transplanted around the abdominal aorta of ApoE-/- recipient mice. Twelve weeks later, the occurrence and progression of AS were assessed. A HFD was found to significantly exacerbate the inflammatory characteristics of PVAT. However, PVAT transplantation did not affect the body weight, fat composition, lipid levels or glucose/insulin sensitivity of the recipient mice. Transplantion of PVAT from obese animals around the abdominal aorta significantly accelerated AS progression and notably increased vascular stiffness. Furthermore, transplanting obese PVAT aggravated endothelial inflammatory responses and the instability of atherosclerotic plaques. Obesity enhanced the inflammatory characteristics of PVAT. This inflammatory PVAT exacerbated endothelial inflammation through paracrine/endocrine mechanisms, thereby accelerating AS progression. Therefore, PVAT is expected to become a new target for the prevention and treatment of AS in the future.