Research identifies a possible therapeutic target for clogged arteries” New work led by Carnegie’s Meredith Wilson and Steve Farber identifies a possible therapeutic target for clogged arteries and other health risks that stem from an more than harmful fats within the bloodstream. Their findings are published by PLOS Genetics.
disease occurs when lipids from the plasma are deposited within the walls of blood vessels, ultimately restricting blood flow,” explained Farber, who focuses on elucidating how cells process lipids. “This complex disease affects a few third of the world’s population, so improving our understanding of the mechanisms that regulate the amount of blood lipids has important public health implications.”
also called lipids, like cholesterol and triglycerides are shuttled round the cardiovascular system by a protein called Apolipoprotein-B, or ApoB for brief . These complexes of lipid and protein are called ApoB-containing lipoproteins and are essential for transporting lipids from the intestine and liver to the tissues of the body. However, because they will also cause disorder , they’re commonly referred to as “bad cholesterol.”
In this new research:-
Wilson, Farber and their colleagues–including Carnegie’s Aidan Danoff, Monica Hensley, Vanessa Quinlivan, James Thierer and Frederick Tan–focused on a protein that’s critical for the synthesis of ApoB-containing lipoproteins. This protein, called MTP, or microsomal triglyceride transfer protein, is very conserved in animals, from insects to humans. MTP loads lipids onto ApoB, a key initial step within the synthesis of ApoB-containing lipoproteins.
MTP can transfer differing types of lipids to ApoB, including triglycerides, which are a serious source of energy, and phospholipids, the building-blocks of membranes within the cell. However, the researchers revealed for the primary time a mutation in MTP that blocks the loading of triglycerides, but not phospholipids, onto ApoB.
mutations in MTP that prevent both transfer functions of the protein cause a syndrome , during which the intestines have difficulty absorbing fats and fat-soluble vitamins from the diet. this will end in gastrointestinal distress or more serious problems, like malnutrition or severe weight loss. However, zebrafish with this newly identified mutation don’t exhibit malabsorption or growth defects, because they will still transfer phospholipids to form ApoB-containing lipoproteins.
MTP has been considered a possible therapeutic target to assist lower triglyceride levels within the blood and stop disorder . However, the prevailing chemical inhibitors of MTP are too effective and block all MTP function, which may cause intestinal fat malabsorption and a dangerous accumulation of fat within the liver.
“Our study opens the door for the planning of more specific MTP inhibitors that mimic this new mutation and selectively block triglyceride transfer to ApoB,” concluded Wilson. “Our data suggests that this sort of inhibitor could reduce circulating triglyceride levels without the danger of unpleasant and high side effects within the intestine and liver.”