The rat Tollip sequence contains 8 lysines as potential sumoylation sites, and it is possible that the sumoylated bands immunoprecipitated with Tollip are only due to SUMO-1 modification of the protein. However, different covalent modifications and, in particular, polyubiquitylation may occur in lysine residues either competing with each other for the same site or independently regulated by events that depend on the target of interest. Although sumoylation does not usually target proteins to destruction, it has been recently shown that sumoylated proteins may become targets of E3 ubiquitylation ligases for proteosomal degradation. We cannot MLN4924 exclude that at least part of the sumoylated Tollip has a proteosomal destiny. The strong increase of the anti-SUMO-1 abs staining shown in figure 3C indicates that the overexpression of Tollip activates the overall cellular sumoylation of the proteins, thus suggesting a rather general role of Tollip in this process. Tollip sumoylation and its interaction with Ubc9 suggest a function of Tollip as a ligase. Conversely, the interaction of Tollip with three different members of the PIAS ligase family favours the idea of a sumoylation adaptor. Adiponectin augments endothelial NO production , inhibits ox-LDL–induced endothelial ROS generation , suppresses the expression of endothelial adhesion molecules , attenuates leucocyte-endothelium interactions and protects endothelial cells from apoptosis. Furthermore, adiponectin inhibits macrophage activation and foam cell formation , promotes the clearance of early apoptotic cells by macrophages , inhibits smooth muscle cell proliferation and antagonizes the stimulatory effect of TNF-a on vascular smooth muscle cell calcification. The present study has several strengths and limitations. Our data support the concept that adiponectin is an important marker in the pathogenesis of atherosclerosis since adiponectin remains significantly associated with plaque morphology in a fully adjusted multivariate model containing age, sex, BMI, hypertension, diabetes mellitus, smoking, family history of CAD, LDL-C, HDL-C, triglycerides, hsCRP, medication and PAT volume. However, since this was an association study, our study does not establish a causal relationship between adiponectin and coronary plaque morphology. Furthermore, the clinical implications of our results still need to be determined. There are conflicting epidemiological data regarding the role of adiponectin in atherosclerosis with some studies showing strong inverse associations between adiponectin levels and CAD and others failing to detect any association. When these forms infect a vertebrate host, they invade host cells and differentiate into amastigotes, which then divide in the cell cytoplasm and differentiate again into trypomastigotes, passing through a transient epimastigote-like stage termed the intracellular epimastigote. The main transmission route of the parasite is via insect vector bites on any region of the host skin.