Scientists Manipulate Fat Metabolism in Animals to Prevent Main Cause of Heart Attacks

Scientists at Johns Hopkins University discovered a molecular inhibitor in lab mice and rabbits that could provide a new target for developing drugs to prevent atherosclerosis (the main cause of heart attacks) in humans.

Atherosclerosis is a type of arteriosclerosis that refers to the process of fatty substances, cholesterol, cellular waste products, calcium and fibrin building up in the inner lining of an artery. The artery blockage can result in either a heart attack or stroke.

The Johns Hopkins University scientists published their study in the journal Circulation on April 7; they identified and stopped the fat and sugar molecule, glycosphingolipid (GSL), from producing abnormal cholesterol. They used an existing man-made compound called D-PDMP to block the GSL molecule and found that the process prevented the development of heart disease in the experimental mice and rabbits who were fed a high-fat and high-cholesterol diet.

D-PDMP, short for D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, is typically used as an inhibitor of glycosphingolipids. It has previously been found to alter the cellular cholesterol homeostasis. When applied to the animals, D-PDMP lowered the animals' levels of low-density lipoprotein (LDL), also known as "bad cholesterol"; provided a surge in high-density lipoprotein (HDL), also known as "good cholesterol"; and led to a drop in triglyceride levels, which is another type of plaque-building fat.

"Atherosclerosis is a multi-factorial problem that requires hitting the abnormal cholesterol cycle at many points. By inhibiting the synthesis of GSL, we believe we have achieved exactly that," said the study's lead investigator Subroto Chatterjee, Ph.D., in a news release.

The scientists conducted other experiments with the animals, but the final set of trials provided valuable information. The researchers fed two groups of healthy rabbits high-fat diets, with half of them receiving D-PDMP treatment and half not. The rabbits who were not treated with the man-made compound had their cholesterol levels skyrocket 17-fold, and they developed signs of atherosclerosis. Those who were treated had their cholesterol levels remain the same or near-normal with no signs of atherosclerosis.