Scientists in Finland discovered that the low-expression variant of fatty acid-binding protein 4 (FABP4), which is particularly common among Finns, reduces the risk of heart attack and stroke. The team believes their work reveals a promising new way to customize a potentially preventive drug for atherosclerosis.

The study (“The Low-Expression Variant of Fatty Acid-Binding Protein 4 Favors Reduced Manifestations of Atherosclerotic Disease and Increased Plaque Stability”), which involved researchers at the University of Helsinki, the Helsinki University Central Hospital, the Wihuri Research Institute, and the National Institute for Health and Welfare, was published in Circulation: Cardiovascular Genetics.

The finding indicates that people who have inherited the genetic variant reducing the expression of FABP4 from both parents have eight-fold lower odds for myocardial infarction than the rest of the population. The group also learned that patients with carotid stenosis who carried the protective gene variant suffered from brain ischemia three times less frequently than carotid stenosis patients without the gene variant.

“It could be that reduced cell stress in the stenosis, attenuated inflammation, as well as reduced accumulation of cholesterol and other lipids in the arteries help keep atherosclerosis asymptomatic among the gene carriers,” explained Jani Saksi, a researcher in the molecular neurology research program at the University of Helsinki.

Tests on laboratory animals have previously shown that an orally ingested drug suppressing FABP4 activity effectively slows down the progression of atherosclerosis and even reduces existing stenoses. The phenomenon has not yet been studied in humans.

The Finnish study is the first to detect a link between the FABP4 variant and lower total cholesterol levels in the blood. The decrease in serum total cholesterol levels was the most pronounced in obese subjects who had inherited the gene variant from both parents. In fact, obese carriers of the gene variant show fewer clinical markers of early atherosclerosis and lower levels of stenosis than the rest of the population.

“Our results reveal FABP4 as a novel variant affecting serum total cholesterol levels and cardiovascular risk. A therapeutic regimen reducing FABP4 expression within the atherosclerotic plaque may promote lesion stability through modulation of ER stress signaling, and attenuation of apoptosis, lipid burden, and inflammation,” wrote the investigators.

“These findings suggest that FABP4 could be a new potential target for drug development aiming to prevent lethal and disabling myocardial and cerebral infarctions induced by atherosclerosis,” continued Saksi. “The inhibition of FABP4 activity, especially among obese people in the risk group for atherosclerosis, may prove to be an important method for reducing these individuals' risk for cardiovascular diseases.”

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