Clinical Implications of Visfatin/PBEF/Nampt for Development of Vascular Inflammation and Atherosclerosis

The adipose tissue is an endocrine organ

The adipose tissue is no longer considered a mere energy depot but a real active endocrine organ that produces a heterogeneous series of bioactive factors, the so-called adipokines. Adipokines can act locally within the adipose tissue, but they are also released to the systemic circulation, therefore reaching distant organs. Adipokines are comprised of cytokines and chemokines, such as tumor necrosis factor (TNF)-α, interleukins (IL), or monocyte chemoattractant protein (MCP)-1, vasoactive and coagulation factors, such as angiotensinogen or plasminogen activator inhibitor-1, (PAI-1), and proteins more specifically secreted by the adipose tissue, such as leptin or adiponectin [1]. While leptin was first described more than a decade ago, the number of the adipokine family members has notably increased in the last years with new molecules such as resistin, visfatin, apelin, chemerin, omentin, or retinol binding protein-4 among others [2, 3].

Abstract

In the last years, the adipose tissue has been acknowledged as an endocrine organ that releases a heterogeneous series of compounds, the so-called adipokines. In 2005, visfatin was first identified as a new adipokine with insulin-mimetic properties, identical to the pre-B cell colony-enhancing factor (PBEF) and exhibiting intrinsic nicotinamide phosphoribosyltransferase (Nampt) enzymatic activity. For this reason, this adipocytokine is currently termed visfatin/PBEF/Nampt. The circulating levels of visfatin/PBEF/Nampt are elevated in metabolic conditions, such as obesity and type 2 diabetes, and although this observation is subject to controversy, they positively correlate with markers of systemic inflammation. In the context of cardiovascular diseases, visfatin/PBEF/Nampt is emerging as a new clinical marker of atherosclerosis, endothelial dysfunction, and vascular damage with a potential prognostic value. A growing bulk of evidence further unveils that visfatin/PBEF/Nampt can not only be a clinical marker, but also an active player in promoting vascular inflammation and atherosclerosis. Hence, through its actions on cytokine and chemokine secretion, macrophage survival, leukocyte recruitment by endothelial cells, vascular smooth muscle inflammation, and plaque destabilization, visfatin/PBEF/Nampt arises as an active player in plaque development and progression. Further in depth research is required to understand the mechanisms mediating the cellular actions of this adipocytokine and to identify the factors that regulate its cellular synthesis and release in different clinical situations. Such knowledge will help determine whether visfatin/PBEF/Nampt can represent a valuable therapeutical target in the context of cardio-metabolic diseases.

Keywords

adipocytokine, obesity, diabetes mellitus, vascular, inflammation, endothelial dysfunction, atherosclerosis