Proinflammatory circulating molecules in peripheral arterial disease.

Peripheral arterial disease (PAD) affects about 5% of the elderly population in the western world. It has been reported that PAD is associated with elevated plasma levels of the inflammatory markers. The goal of this review is to describe which proinflammatory molecules may play a role in PAD development, C-reactive protein, fibrinogen, pro-inflammatory cytokines, adhesion molecules and matrix metalloproteinases have been reported to be involved. High serum levels of both C-reactive protein and fibrinogen have been shown to be significantly associated with increasing severity of PAD. Among cytokines, IL-6 is one of the most studied in PAD. IL-6 is well recognized for its role in the acute phase inflammatory response which is characterized by production of a variety of hepatic proteins termed acute phase proteins. It has been shown that increased serum concentrations of several markers of the acute response, including IL-6, are elevated in patients with type 2 diabetes. These patients have a two-fold risk of PAD compared to those without type 2 diabetes. The G(-174)C IL-6 polymorphism has been suggested to influence IL-6 release, and its possible influence on PAD development among individuals with type 2 diabetes is discussed in this review. Further study of these molecules is justified as they appear to be involved in the development of PAD.