Insulin Degrading Enzyme And Its Role In Atherosclerosis

The type-A scavenger receptor (SR-A) plays a major role in the uptake of modified lipoproteins leading to foam cell formation and fatty streak development in artery walls. Our lab previously showed that a peptide known as insulin degrading enzyme (IDE) is able to bind the SR-A cytoplasmic domain in vitro. The present study provides evidence that male low density lipoprotein receptor-null (LDLr-/-) mice on a high fat diet, generate significantly more atherosclerotic lesion in aortic root and the aortic intimal surface when reconstituted with IDE-null (IDE-/-) bone marrow derived cells compared to those reconstituted with wild type bone marrow. Total serum cholesterol and the LDLr cholesterol fraction was also significantly increased in male LDLr-/- mice reconstituted with IDE-/- bone marrow. Macrophages procured from IDE-/- mice showed no difference in uptake of modified LDL compared to wild type cells but may be able to accumulate more cholestertyl ester than wild type cells. Our findings reveal that IDE expression likely exerts an anti-atherogenic effect via cholesterol metabolism, although further in vitro experiments are required to elucidate an exact mechanism