Atherosclerosis is one of the leading causes of cardiovascular disease in the world. It is a condition in which arteries narrow and harden due to plaque buildup, and can lead to heart attacks and other serious events, often without obvious symptoms until it is too late.
A new study published in the journal Circulation Research proposes a different way of looking at the problem, shifting the focus to two lipid molecules that play an important role in blood vessel health: sphingosine-1-phosphate (S1P) and ceramides.
These two molecules are part of the same “family” (that of sphingolipids), but they act in opposite ways: S1P tends to protect blood vessels, while ceramides are associated with inflammation and cellular damage. Until now, ceramide accumulation has been thought to be a key factor in the development of atherosclerosis. But according to researchers led by Onorina L. Manzo, things may be more complex.
The researchers used an animal model to observe what happens to endothelial cells (those lining the inside of blood vessels) when they are subjected to mechanical stress, such as that caused by irregular blood flow. They saw that under these conditions the cells tend to produce more S1P and less ceramide, through a process involving a protein called NOGO-B.
Notably, in mice in which NOGO-B was genetically cleared from endothelial cells, the development of atherosclerotic plaques was much more limited. The arteries showed less inflammation, more stable plaques, and a lower presence of harmful immune cells.
The most interesting result of the study was that the absence of ceramide accumulation still did not prevent the development of the disease: therefore, they are not the sole cause of the damage. On the contrary, shifting the balance of cellular metabolism toward S1P production seemed to have a protective effect.
This could open up new possibilities for both the diagnosis and treatment of atherosclerosis. On the one hand, measuring S1P and ceramide levels in the blood could help predict cardiovascular risk better than cholesterol alone. On the other, intervening in sphingolipid metabolism-for example, selectively inhibiting NOGO-B-could become a new therapeutic strategy.
As is often the case with laboratory studies, there is still a long way to go before these results can be applied in humans. More studies will be needed to better understand the mechanisms involved and to evaluate the efficacy and safety of possible drugs.
The article A new way to understand (and perhaps treat) atherosclerosis comes from TheNewyorker.
