Inflammatory mechanisms in the pathogenesis of cardiovascular Disease

Dendritic cells (DCs) of the immune system are present in the normal human arterial wall and increase in atheroma, and appear in the arteries of laboratory rodents in experimental atherogenesis and upon traumatic injury. Rosiglitazone reduces the inflammatory response to experimental arterial injury and the intercellular contacts of DCs in this condition. Dendritic cells can differentiate from monocytes and haematopoietic stem cells, including CD133+ highly immature ones. Rosiglitazone promotes the differentiation of Langerhans cells and inhibits that of other DC types from CD133+ hematopoietic precursors. In vitro experiments on human cells2 have demonstrated that monocyte derived DCs adhere to vascular smooth muscle cells (VSMCs) with reciprocal stimulation: DCs are induced to mature and VSMCs are induced to increase migratory activity. Adhesion is enhanced by stimulation of VSMCs with IFN-gamma and TNF-alpha and is inhibited by pretreatment of those cells with rosiglitazone and atorvastatin. The increased adhesion is mediated by CD54(ICAM-1)/CD11c and CD106(VCAM-1)/CD28; the cell interaction is mediated also by soluble molecules, including TNF-alpha secreted by DCs, IL-6 secreted by VSMCs and MCP-1 secreted by both cell types. In an in vivo rat model it has been shown that adhesion between DCs and VSMCs occurs also during the response to experimental carotid injury. Preliminary evidence in this respect has been found also for human atheroma. Therefore DCs may be candidate to a major role in the onset and progression of vascular inflammation, even independent of specific immune responses, and may be target for therapy