The Role of Obesity, Inflammation and Sphingolipids in the Development of an Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a local dilatation of the vessel equal to or exceeding 3 cm. It is a disease with a long preclinical period commonly without any symptoms in its initial stage. Undiagnosed for years, aneurysm often leads to death due to vessel rupture. The basis of AAA pathogenesis is inflammation, which is often associated with the excess of adipose tissue, especially perivascular adipose tissue, which synthesizes adipocytokines that exert a significant influence on the formation of aneurysms. Pro-inflammatory cytokines such as resistin, leptin, and TNF alpha have been shown to induce changes leading to the formation of aneurysms, while adiponectin is the only known compound that is secreted by adipose tissue and limits the development of aneurysms. However, in obesity, adiponectin levels decline. Moreover, inflammation is associated with an increase in the amount of macrophages infiltrating adipose tissue, which are the source of matrix metalloproteinases (MMP) involved in the degradation of the extracellular matrix, which are an important factor in the formation of aneurysms. In addition, an excess of body fat is associated with altered sphingolipid metabolism. It has been shown that among sphingolipids, there are compounds that play an opposite role in the cell: ceramide is a pro-apoptotic compound that mediates the development of inflammation, while sphingosine-1-phosphate exerts pro-proliferative and anti-inflammatory effects. It has been shown that the increase in the level of ceramide is associated with a decrease in the concentration of adiponectin, an increase in the concentration of TNF alpha, MMP-9 and reactive oxygen species (which contribute to the apoptosis of vascular smooth muscle cell). The available data indicate a potential relationship between obesity, inflammation and disturbed sphingolipid metabolism with the formation of aneurysms; therefore, the aim of this study was to systematize the current knowledge on the role of these factors in the pathogenesis of abdominal aortic aneurysm.