The present invention relates to methods for the production of atheroprotective vesicles. The invention is based on the finding that endothelial cells wherein the activity of the transcription factor KLF2 is induced and/or enhanced surprisingly produce and/or secrete vesicles enclosing various atheroprotective microRNAs, in particular microRNAs of the microRNA-cluster miR-143/145. Thus, the present invention discloses methods for the production of vesicles derived from atheroprotective endothelial cells and the vesicles produced by the disclosed methods. Furthermore artificially produced vesicles enclosing the atheroprotective microRNA composition according to the invention are provided. The vesicles of the present invention are useful in the treatment and prevention of atherosclerotic diseases, such as acute coronary syndromes, plaque rupture, aneurysms, in-stent restenosis, ischemic diseases and heart failure.
