Antibodies against atherosclerosis
Researchers from the University of California at San Diego, working under the guidance of Professor Joseph Witztum, have developed a method for blocking inflammation of vascular walls in a mouse model using antibodies synthesized in the body that bind to oxidized phospholipids (OxPL) - molecules of the cell surface that undergo modification under inflammatory conditions. Even in conditions of a fat-rich diet, antibodies prevented the formation of atherosclerotic plaques on the inner walls of the arteries and the development of the consequences of atherosclerosis.
Some phospholipids – molecules that are the main building material of cell membranes – are modified by the action of reactive oxygen species to form oxidized phospholipids. This phenomenon is especially characteristic of inflammatory conditions, such as atherosclerosis, a distinctive feature of which is the formation of plaques blocking the lumen of the vessel. Previously, researchers had no tools at their disposal to influence the oxidation of phospholipids, which would allow studying the role of these molecules in the development of inflammation and atherosclerosis.
According to Professor Witztum, in conditions of inflammation, oxidized phospholipids always appear on cell membranes. This does not mean that they are the cause of the development of the inflammatory process, but it is obvious that these compounds play an important role in its aggravation.
The authors solved this problem by creating genetically modified mice with 2 features: a mutation that causes their predisposition to the development of atherosclerosis, and the ability to synthesize an E06 antibody fragment that binds to oxidized phospholipids, preventing the development of inflammation. These animals were kept on a fat-rich diet.
The aorta of a mouse model of atherosclerosis, which was kept on a fat-rich diet for 12 months (above), is covered with significantly more plaques (bright red) than the aorta of mice of the same line, in whose body anti-inflammatory antibodies E06 are produced (below).
Compared with control group animals also predisposed to the development of atherosclerosis, mice with E06 antibodies had atherosclerosis expressed by 28-57% less even when consuming a large amount of fat during the year and against the background of high cholesterol concentration in the blood. These antibodies also reduced the likelihood and severity of aortic valve calcification, fatty liver degeneration and hepatitis. In addition, the serum of experimental mice had a 32% decrease in the level of amyloid A– a marker of systemic inflammation.
Separately, it should be noted that the E06 antibodies increased the life expectancy of animals. All experimental animals lived to the age of 15 months, whereas for the control group this indicator was only 54%.
The authors are currently testing E06 antibodies on mouse models of other human inflammatory diseases, such as osteoporosis and non-alcoholic fatty liver dystrophy.
Article by Xuchu Que et al. Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice published in the journal Nature.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of California San Diego: Antibody Blocks Inflammation, Protects Mice from Hardened Arteries and Liver Disease.