Title

 

Authors

A. Parenti^1,2, S. Paccosi¹ , C. Musilli ¹, L. Pala ³,  C.M. Rotella ³ , A. Mugelli ^1,2
 
1Dept. of Pharmacology, ²CIMMBA, Section of Endocrinology, ³Department of Clinical Pathophysiology, University of Florence, Florence, Italy.

 

Abstract

Vascular remodeling is a chronic multi-factorial disease in which systemic or local inflammatory pathogenetic mechanisms play a key role. It has been become evident that dendritic cells (DCs) are also involved in driving the chronic vascular inflammation which characterizes this disease (Bobryshev, 2005). The hypothesis that DC are critical for atherogenesis is also supported by the fact that statin application leads to a lower number of DC in atherosclerotic plaques (Yilmaz et al., 2004). However, their role in the patoghenesis of vascular remodeling and their relationship with vascular wall cells is still unclear. Recently, clinical and preclinical data highlighted the role of adipose tissue in the development of a systemic inflammatory state, by releasing adipokines which increase inflammation leading to insulin resistance and atherosclerosis (Maury et al., 2010). The aim of this study was to characterize DCs in obese patients with insulin-resistance and to study their relationship with vascular smooth muscle cells. Circulating DCs and moncyte-derived DCs (Mo-DC) of obese and diabetic patients were characterized, and their interaction with human coronary smooth muscle cells (CASMCs) were studied. In the present study were enrolled only post-menopausal women having a median age of  70 years with a BMI>30 and who were diagnosed as insulin resistance. The different subsets of DCs in peripheral blood were detected by direct immunofluorescence staining with a panel of monoclonal antibodies that recognize the different lineage markers (BDCA1,2,3,4) and the subsequent cytofluorimetric analysis with a flow cytometer EPICS XL (Beckman Coulter). Mo-DC were obtained ex vivo by CD14⁺ cells isolated by patients, cultured for 6 days in medium supplemented with GM-CSF and IL-4 followed by a further maturation stimuli (IL-6, IL1β, TNF-α). The analysis of circulating DCs revealed a significant increase of myeloid subsets (BDCA-1-3) and with a lesser extent plasmacytoid one (BDCA-2), compared to healthy donors. However, a significant decrease of Mo-DCs were obtained by circulating precursors isolated from diabetic patients when compared to control. We than studied the interaction between DCs and vascular smooth muscle cells by means adhesion experiments. Mo-DCs obtained from obese and diabetic patients displayed an higher ability to adhere to coronary SMCs  compared to healthly DCs.
These preliminary data suggest that in a condition of insulin-resistance and obesity there is an up-regulation of myeloid DCs that might contribute to pathological vascular remodeling.
 
Bobryshev YV. Eur Heart J. 2005;26(17):1700-4.
Yilmaz A et al., Atherosclerosis. 2004 Sep;176(1):101-10.
Maury E et al., Mol Cell Endocrinol. 2010 Jan 15;314(1):1-16.