Human species-specific loss of CMP- N -acetylneuraminic acid hydroxylase enhances atherosclerosis via intrinsic and extrinsic mechanisms

Significance Cardiovascular disease (CVD) events like heart attacks and strokes due to atherosclerotic narrowing of arteries are the commonest cause of worldwide deaths, but many first-time events occur in individuals without known risk factors. In contrast, such events are extremely rare in other animals despite some of the same risk factors. While environmental and behavioral factors likely contribute to the difference, we show here that a human-specific genetic mutation affecting cell-surface molecules called sialic acids may be one other factor. We also show that the same mutation can help explain the apparently human-specific increased risk of CVD events associated with red meat consumption. The humanized mouse systems we present could be explored as models for future studies of atherosclerosis.