Atherosclerosis is a chronic inflammatory disease of the arteries characterized by fatty streak formation due to an accumulation of lipids, triglycerides, cholesterols and lipoproteins in the intima layer. Autophagy is one of the molecular processes involved in atherosclerosis. To date studies show that autophagy deficiency may be pro-atherogenic and the role of autophagy in smooth muscle cells, macrophages and endothelial cells has been investigated. However, no studies addressed the effect of autophagy on CD4+Tregs subsets playing a role in plaque formation and development. The present project aims to better clarify the role played by autophagy in Tconv/Tregs homeostasis in human atherosclerotic plaques. We characterized lymphocyte populations in different types of lesion by using flow cytometry. In particular, we detected OX40 as marker for conventional T cells promoting division and survival of effector and memory populations and pS6, a marker for an active mTOR pathway and autophagy detection. The understanding of the role of autophagy as a further mechanism underlying lymphocytes stability may open new therapeutic avenues for atherosclerosis.
The present project aims at clarifying if autophagy is involved in the induction and in the maintenance of Treg cells and if in the APOE knock-out model this mechanism is alterated thus being involved in the pathogenesis of atherosclerosis. The modulation of autophagy may be helpful for atherosclerosis therapy.
We evaluated carotid endarterectomies Atherosclerotic lesions have been divided in six groups by American Heart Association and plaques are considered advanced by histological criteria when accumulations of lipid, cells, and matrix components, including minerals, are associated with structural disorganization, repair, and thickening of the intima, as well as deformity of the arterial wall.
The therapeutic use of Tregs by adoptive transfer in atherosclerosis represents a valid therapeutic option but there are several difficulties which hopefully in the future should be circumvented. The mechanisms driving Tregs induction and stability have been extensively studied but the comprehension of an additional mechanism such as autophagy as a further mechanism underlying T reg induction and stability may open new therapeutic avenues. By using pharmacological and more specific genetic approaches targeting specific proteins involved in the autophagic cascade it would be possible in the future to improve Tregs induction, maintenance and functionality and exploit them for atherosclerosis therapy.
To understand the involvement of autophagy in Treg cells in atherosclerotic plaques, we will check the expression of LC3 (as marker for autophagy) and pS6 (as mTOR activator marker) by FACS analysis.