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Changes of lysosomes in the earliest stages of the development of atherosclerosis
Authors:Yuri V Bobryshev  Tatyana A Shchelkunova  Ivan A Morozov  Petr M Rubtsov  Igor A Sobenin  Alexander N Orekhov  Alexander N Smirnov
Institution:1. Faculty of Medicine, School of Medical Sciences, University of New South Wales, , Kensington, NSW, Australia;2. School of Medicine, University of Western Sydney, , Campbelltown, NSW, Australia;3. Institute for Atherosclerosis Research, Skolkovo Innovation Center, , Moscow, Russia;4. Biological Faculty, Lomonosov Moscow State University, , Moscow, Russia;5. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, , Moscow, Russia;6. Russian Cardiology Research and Production Complex, , Moscow, Russia;7. Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, , Moscow, Russia
Abstract:One of hypotheses of atherosclerosis is based on a presumption that the zones prone to the development of atherosclerosis contain lysosomes which are characterized by enzyme deficiency and thus, are unable to dispose of lipoproteins. The present study was undertaken to investigate the characteristics and changes of lysosomes in the earliest stages of the development of atherosclerosis. Electron microscopic immunocytochemistry revealed that there were certain changes in the distribution of CD68 antigen in lysosomes along the ‘normal intima‐initial lesion‐fatty streak’ sequence. There were no significant changes found in the key mRNAs encoding for the components of endosome/lysosome compartment in initial atherosclerotic lesions, but in fatty streaks, the contents of EEA1 and Rab5a mRNAs were found to be diminished while the contents of CD68 and p62 mRNAs were increased, compared with the intact tissue. The study reinforces a view that changes occurring in lysosomes play a role in atherogenesis from the very earlier stages of the disease.
Keywords:atherosclerosis  initial lesion  fatty streak  aorta  intima  lysosomes  CD68
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