Vasoactive Factors and Inflammatory Mediators Produced in Adipose Tissue

Abstract

In the search for mechanisms of obesity-mediated vascular pathology, attention has been focused on the role played by adipose tissue, a multifunctional organ involved not only in fat storage but also in the production of numerous hormones, growth factors, and cytokines with pleiotropic features. In the last decade the list of adipose-derived factors shown to be implicated either directly or indirectly in the regulation of vascular homeostasis through effects on blood pressure, inflammation, atherogenesis, coagulation, fibrinolysis, angiogenesis, proliferation, apoptosis, and immunity has increased at a phenomenal pace. By definition, adipocytokines are cytokines produced by adipocytes. Although adipose tissue secretes a wide variety of factors, strictly speaking, not all of them can be contemplated as cytokines. Interleukin-6, tumor necrosis factor-α, leptin, adipsin, resistin, adiponectin, and visfatin fall within the category that satisfies the stricter requirements to be properly classified as adipocytokines. However, the less strict term of adipokines has been coined to include a wider range of factors such as PAI-1, C-reactive protein, monocyte chemoattractant protein-1, serum amyloid A, and vascular endothelial growth factor, among others. Adipokines are known to contribute to the low-grade inflammation state observed in obese patients at the same time as participating in the development of obesity-related comorbidities, such as insulin resistance, metabolic syndrome, and atherogenesis. The molecular mechanisms linking the adiposity-inflammation-immunity cluster are complex. The triad of obesity-insulin resistance-cardiovascular disease is interwoven in a setting of inflammation, endothelial dysfunction and atherosclerosis in which adipokines act as markers of the acute phase reaction at the same time as being directly involved as causative factors in an extensive crosstalk between adipocytes and elements of the stroma vascular fraction. The current knowledge in this field is reviewed with a broad perspective approach.