Protein Interactions Help Prevent Arterial Blockage

The protein alpha-1-microglobulin (A1M) helps to prevent development of arteriosclerosis by inhibiting the oxidation of LDL (low-density lipoproteins) that is induced by the combination of myeloperoxidase (MPO) and hydrogen peroxide.

MPO, a heme-containing enzyme that catalyzes the production of free radicals and hypochlorite, is released by neutrophils during the inflammatory response to bacterial infections. MPO-induced low-density lipoprotein (LDL)-oxidation in blood has been suggested as a causative factor in atherosclerosis. A1M, which binds and degrades heme, is a radical scavenger as well as a reductase. A model has been proposed in which A1M is described as a circulating “waste bin” which continuously removes free radicals and oxidizing agents, particularly heme, from the tissues. It is subsequently transported to the kidneys, where it is broken down. The protein is therefore believed to protect cells and tissues against the damage that is induced by abnormally high concentrations of free hemoglobin and/or reactive oxygen species.

Investigators at Lund University (Sweden) studied the interaction between A1M and MPO in an in vitro model system. They reported in the February 3, 2015, online edition of the journal Frontiers in Physiology that A1M was cleaved proteolytically, with formation of t-A1M, after exposure to MPO, and that t-A1M contained iron and heme-degradation products. The reaction was dependent on pH, time, and concentration of substrates and a pH-value around 7 was shown to be optimal for cleavage. Furthermore, A1M inhibited MPO- and hydrogen peroxide-induced oxidation of LDL.

Senior author Dr. Bo Akerstrom, professor of medicine at Lund University, said, "By studying and testing A1M's properties in relation to LDL and MPO, we discovered that A1M can clean and reduce oxidized blood fats from LDL, as well as taking care of the dangerous substances from MPO and breaking them down. This means that A1M protects against damage to the molecules that we know is a cause of atherosclerosis. The next step is animal experiments, as well as analysis of human tissues. We want to study the blood to see if there is a link between the level of A1M, the concentration of oxidized blood fats, and the development of atherosclerosis. If this correlation exists, which I believe it does, I can imagine that it will be possible in the future to develop a preventive drug that reduces the risk of atherosclerosis. It is not impossible that future patients could receive one dose of A1M per month to clean the blood vessels."

Related Links:
Lund University