Selective reduction in the sphingomyelin content of atherogenic lipoproteins inhibits their retention in murine aortas and the subsequent development of atherosclerosis.

ABSTRACT:

Objective

We used the sphingomyelin (SM) synthase 2 (Sms2) gene knockout (KO) approach to test our hypothesis that selectively decreasing plasma lipoprotein SM can play an important role in preventing atherosclerosis.

Methods and results

The sphingolipid de novo synthesis pathway is considered a promising target for pharmacological intervention in atherosclerosis. However, its potential is hampered because the substance's atherogenic mechanism is not completely understood. We prepared Sms2 and apolipoprotein E (Apoe) double-KO mice. They showed a significant decrease in plasma lipoprotein SM levels (35%, P<0.01) and a significant increase in ceramide and dihydroceramide levels (87.5% and 27%, respectively; P<0.01) but no significant changes in other tested sphingolipids, cho

SUBMITTER: Fan Y 

PROVIDER: S-EPMC3426833 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature