Salk's Breakthrough: Rethinking Heart Disease Beyond Cholesterol

**Salk Institute researchers have uncovered a new dimension to understanding atherosclerotic cardiovascular disease (ASCVD) by studying the role of sphingolipids, a class of fats, in arterial plaque formation.** Traditionally, cholesterol was considered the primary culprit behind heart disease, leading to the development of statins and lifestyle adjustments aimed at reducing cholesterol levels. However, this new research shows that sphingolipids, particularly those derived from trans fats, play a significant role in ASCVD. The study involved a longitudinal investigation of mice fed high-fat diets without additional cholesterol, using metabolic tracing and dietary manipulation. The research found that trans fats incorporate into sphingolipids through a protein called SPT, which promotes the excess secretion of lipoproteins, like VLDL, contributing to plaque buildup in arteries. Conversely, cis fats, naturally present in foods like fish, do not provoke the same response due to their structural differences. The team utilized techniques like pharmacological intervention to explore the connection between trans fats, sphingolipids, and ASCVD. They discovered that inhibiting SPT can reduce the harmful effects of trans fats. These findings position sphingolipid metabolism as a critical target for developing new non-statin drugs for cardiovascular disease. Despite global efforts, trans fats remain a threat to billions, making this research pivotal in improving heart health strategies. _Professor Christian Metallo emphasizes the potential of personalized medicine through the understanding of individual dietary and genetic factors, shedding light on a future where novel treatments for ASCVD could be developed._