The use of electron microscopy for the detection of autophagy in human atherosclerosis.

The term autophagy broadly refers to a set of biological processes that mediate the clearance of damaged and/or dysfunctional subcellular structures. Central to this pathway is the formation of double-membrane vesicles that engulf cytoplasmic components and deliver them to the lysosomes. In mammalian systems, autophagy is believed to occur constitutively at basal rates but it can be also involved in a plethora of different pathological conditions. To date, however, its occurrence in human atherosclerosis remains incompletely characterized and often unappreciated probably due to technical limitations. Hitherto, the activation of autophagy in atherosclerosis has been investigated almost exclusively in both in vitro and in vivo disease models and only a few, isolated reports deal with the ultrastructural features of autophagy within human lesional tissues. By using a morphological approach, the present study demonstrated that autophagy is a recurrent feature of human atherosclerosis and occurred in all the main cell types involved in the disease. The autophagic cells were recognizable by the presence of numerous single and double-membraned autophagic structures, clearly distinguishable from the other cytoplasmic vacuoles by virtue of their electron density profiles and their content. These observations provide the first detailed description of the ultrastructural scenario of autophagy in human atherosclerosis.