Weill Cornell Medicine investigators have made a significant discovery in the field of heart disease treatment by uncovering a way to utilize sphingolipids, a type of fat-related molecule, to protect blood vessels from coronary artery disease. Through their research, they found that increasing levels of a specific sphingolipid called S1P in endothelial cells lining the arteries can slow down the progression of this condition in animal models. This groundbreaking study was led by Dr. Onorina Laura Manzo, a postdoctoral researcher in Dr. Annarita Di Lorenzo’s laboratory at Weill Cornell Medicine.
Sphingolipids have long been a subject of mystery in the field of biology, with their exact functions remaining unclear. Recent evidence has shown a correlation between sphingolipids, particularly S1P, and coronary artery disease, as patients with this condition tend to have lower levels of S1P in their bloodstream. The researchers aimed to further investigate the roles of sphingolipids and determine their potential as therapeutic targets, given that coronary artery disease affects millions of individuals and remains a major cause of mortality worldwide.
The team used a unique mouse model to study how stress on arteries, which leads to the development of coronary artery disease, triggers an increase in S1P production in endothelial cells. By eliminating a protein called NOGO-B that inhibits S1P production, the researchers were able to sustain this protective response and make the animals more resistant to coronary artery disease and related mortality. Additionally, the study challenged the prevailing assumption that high levels of ceramides, another group of sphingolipids, are causative factors in coronary artery disease. While ceramide levels in the bloodstream were elevated, their levels in artery-lining endothelial cells remained consistent regardless of disease status, prompting the researchers to reassess their role in the condition.
Overall, the findings from this study pave the way for the development of new drugs that can increase S1P levels to prevent or treat coronary artery disease. By shedding light on the protective effects of sphingolipids in blood vessels, the researchers have opened up a promising avenue for addressing this prevalent and deadly cardiovascular condition. The research was supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, through grant funding, demonstrating the importance of continued investment in cardiovascular research to advance our understanding and treatment of heart diseases.
