Potential Role for Dendritic Cells in Endothelial Dysfunction, Diabetes and Cardiovascular Disease

Abstract: Background: Endothelial dysfunction (ED) is a pathophysiological mechanism present in patients affected by type 2 diabetes (T2DM) supporting the development of cardiovascular disease. Among immune- and inflammatory cells accelerating atherosclerosis, dendritic cells (DC) play a pivotal role, however their pathogenetic mechanism has not been fully clarified, at present. The aim of our review is to explore the relationship between ED, DCs and cardiovascular events. Methods: We analysed the literature in Medline database under ‘‘endothelial function OR dysfunction OR vasodilatation’’, AND ‘‘dendritic cells” OR “innate immunity” OR “adaptive immunity” AND “diabetes” AND “cardiovascular disease” OR “atherosclerosis”. Research articles, systematic reviews and clinical trials have been screened. Results: Both conventional DCs (cDCs) and plasmacytoid cells (pDCs) have been found in the atherosclerotic lesions, together with other pro-inflammatory cells, leading to increase local inflammation. This inflammatory state drives DC interaction with dysfunctional endothelium activating vascular smooth muscle cells. Clinical studies have reported a dysregulation in circulating DC number and function in T2DM patients, especially in those with macrovascular complications, and a significant correlation between reduction in pDCs, TNF-α production and poor glycemic control has been reported. Conclusion: Several studies have proven the prognostic significance of endothelial function and the accumulation of cDCs and pDCs in the arterial intima, thus suggesting their pathogenetic role in atherogenesis. A lack of clinical results is evident, since most observations on human studies are based on circulating measurements despite the fact that different DCs, residing in different tissues, were not detectable in peripheral blood samples. Further preclinical and clinical studies are needed, which should include the measurement of both circulating and tissueresiding DCs simultaneously.