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Research Identifies New Therapeutic Target to Treat Heart Disease

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A potential therapeutic target for the treatment of clogged arteries and other such health complications has been identified by a research published in PLOS Genetics, says an International Business Times report from Singapore. These conditions often occur due the presence of excess harmful fats in the bloodstream.

“Cardiovascular disease occurs when lipids from the blood plasma are deposited in the walls of blood vessels, ultimately restricting blood flow. This complex disease affects about a third of the world’s population, so improving our understanding of the mechanisms that regulate the levels of blood lipids has important public health implications.”
Steve Farber, Lead Author of the Study
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What Has the Study Found?

A protein called Apolipoprotein-B, or ApoB, serves as the vehicle for transportation of fat molecules or lipids in the circulatory system. This combination of the lipid and the protein molecules is known as ApoB-containing lipoprotein and serves to transfer lipids from the liver and the intestine to the tissues of the body. These complexes are also called ‘bad cholesterol’ as they are responsible for heart disease.

Carnegie scientists Farber and Wilson have studied a protein called MTP ( Microsomal Triglyceride Transfer protein), that is critical for the synthesis of ApoB-containing lipoproteins. The MTP is richly conserved in all animals, including insects, and serves to the load lipid molecules on to ApoB during the synthesis of ApoB-containing lipoproteins.

MTP transfers various types of lipids to ApoB, such as triglycerides, which are a rich source of energy, and phospholipids, which constitute the outer membranes of cells. The scientists have discovered a mutation in MTP that hinders the loading of triglycerides on to ApoB, but allows the process for phospholipids.

Previously recognised mutations in the MTP protein had blocked both transfer functions of the protein, causing a malabsorption condition, which led to gastrointestinal distress resulting in malnutrition or severe weight loss.

"The separation of these two transfer functions was unexpected and is important, because high triglyceride levels in lipoproteins are correlated with bad clinical outcomes like diabetes and heart disease," said lead author Wilson.

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What it Means

“Our study opens the door for the design of more specific MTP inhibitors that mimic this new mutation and selectively block triglyceride transfer to ApoB. Our data suggests that this type of inhibitor could reduce circulating triglyceride levels without the risk of unpleasant and serious side effects in the intestine and liver.”
Meredith Wilson, Co-Author of the Study

For a long time, MTP has been considered a prospective therapeutic target in effecting lower triglyceride levels in the blood to reduce the risk of cardiovascular disease. While the existing chemical inhibitors of MTP obstruct both MTP functions leading to intestinal fat malabsorption, this study has identified a new mutation that blocks the increase in triglyceride level without hindering other necessary processes.

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