One of the many great things about being a scientist in Manhattan is that there are enough researchers on this 13.4 mile island to constitute large, specialized groups of scientists, amenable to regular meetings that aren’t able to happen elsewhere. One of my personal favorites (being a lipid researcher myself) is the bi-monthly meeting held by the New York Lipid and Vascular Biology Research Club. This club consists of area lipid researchers from Columbia, Rockefeller, Memorial-Sloan Kettering, Rutgers, NYU, Einstein, Cornell, plus many more (academia and industry alike).
This month’s the topic was Sphingolipids and Sphingomyelinases. Sphingolipids are a class of bioactive lipids that consist of a long chain sphingoid base conjugated to a fatty acid and a polar head group. De novo synthesis of sphingolipids begins in the endoplasmic reticulum, where serine and palmitate condense and undergo a series of reactions to form ceramide. Complex sphingolipids are only formed when ceramide is transported to the Golgi, where additional modifications occur. Sphingolipids function primarily as second messengers regulating a diverse array of biological processes. Some of these processes include response to heat stress, endosytosis, protein trafficking and excytosis, the formation of lipid rafts, calcium homeostasis, longevity, and nutrient uptake. More importantly, defects in sphingolipid metabolism has been linked to several diseases, including cardiovascular disease (atherosclerosis).
This month, Ira Tabas of Columbia University discussed some of his recently published work on the role of acid sphingomyelinase in the progression of early atherosclerotic lesions. The secreted form of acid sphingomyelinase (S-SMase) is an enzyme that hydrolyzes the complex sphingolipid sphingomyelin to form ceramide on atherogenic lipoproteins. The formation of ceramide causes lipoproteins to aggregate, leading to foam cell formation and the progression of atherosclerotic lesions. Dr. Tabas’ work demonstrated that atherogenic mice lacking acid SMase exhibit decreased lipoprotein retention and foam cell formation. Additionally, SMase-deficient atherogenic mice fed a high fat diet had smaller aortic lesions!
This work provides a mechanistic basis for SMase-targeted therapies in the treatment of atherosclerosis. However, as discussed in article, SMase deficiency has been associated with low HDL (good, anti-atherogenic cholesterol) and high LDL (bad, pro-atherogenic cholesterol). Thus, using an inhibitor of sphingomyelin formation may be more appropriate to reduce SMase activity and limit the progression of atherosclerotic lesions.
On a final note, if lipid club strikes your fancy, you are welcome to join! While there is no website for this club, you can be added to the listserve by sending you name and mailing address to mary_ann_makary@merck.com.