A potential breakthrough in the treatment of coronary artery disease has been discovered by investigators at Weill Cornell Medicine. By increasing the levels of a specific type of fat-related molecule called sphingolipid, known as S1P, in the endothelial cells of blood vessels, the researchers were able to slow down the progression of the disease in an animal model. This study, published in Circulation Research on March 8, was led by Dr. Onorina Laura Manzo, a postdoctoral researcher working under the guidance of Dr. Annarita Di Lorenzo, an associate professor of pathology and laboratory medicine at Weill Cornell Medicine. Sphingolipids have long been a subject of mystery in biology, hence their name being derived from the sphinx of ancient mythology. However, recent evidence has shown their significance in coronary artery disease, with lower levels of S1P being observed in patients with this condition. Despite this progress, the exact functions of these lipids in the disease remain unclear.
The researchers in the recent study aimed to gain a deeper insight into the roles of sphingolipids and their potential as therapeutic targets. Despite the presence of cholesterol-lowering medications and other treatments, coronary artery disease remains the primary cause of mortality worldwide, impacting over 20 million individuals in the United States alone.
Through the utilization of an innovative mouse model created by the same research team, it was discovered that stress on arteries related to blood pressure, which can lead to coronary artery disease, triggers an increase in S1P production in endothelial cells as a protective mechanism. While this response is typically temporary, the deletion of NOGO-B protein, which inhibits S1P production, enables the sustained elevation of endothelial S1P production. Consequently, this made the animals significantly more resilient to coronary artery disease and its associated mortality.