Novel Approach to Lowering Cholesterol

Canadian scientists have genetically altered mice to lack either of two pathways through which humans and mice provide lipids for high-density and low-density lipoproteins (HDL and LDL), markedly lowering the levels of cholesterol in their bloodstream.

Both mice in the study did not appear to suffer any ill effects. Alteration of one of the pathways also lowered blood levels of homocysteine by 50%. The results were reported at the annual meeting of the American Society for Biochemistry and Molecular Biology/Union of Biochemistry and Molecular Biology Conference in Boston (MA, USA).

The study focuses on two methods or pathways (CT and PEMT) by which the liver makes phosphatidylcholine (PC), the key building block of cell membranes and an important component of the HDL and LDL that carry fat and cholesterol in the blood stream. The CT pathway contributes about 70% of the PC in liver and the PEMT contributes the other 30%. When the mice were genetically altered so their livers lacked either pathway, they appeared normal and bred normally but in each case their levels of lipoproteins were decreased by as much as half.

This suggests that pharmacologic inhibition of the manufacture of PC in the liver might be a useful approach to lowering LDL in the blood stream, according to Dr. Dennis Vance, Canada research chair in molecular and cell biology of lipids, and colleagues at the University of Alberta (Edmonton, Canadaca) who conducted the study.




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