Published Online
on September 22, 2003

A more recent version of this article appeared on October 7, 2003

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Submitted on October 23, 2002
Revised on June 13, 2003
Accepted on June 18, 2003

Oral Synthetic Phospholipid (DMPC) Raises High-Density Lipoprotein Cholesterol Levels, Improves High-Density Lipoprotein Function, and Markedly Reduces Atherosclerosis in Apolipoprotein E-Null Mice

Mohamad Navab PhD^*, Susan Hama BSc, Greg Hough MS, and Alan M. Fogelman MD

From the Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, Calif.

^* To whom correspondence should be addressed. E-mail: mnavab{at}mednet.ucla.edu.

Background--Lecithin has been widely sold as a dietary supplement. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) is a phospholipid that does not exist in nature and has been used in vitro to study lipid binding. We tested DMPC in vivo in apolipoprotein (apo) E-null mice.

Methods and Results--DMPC or soy or egg lecithin at 1.0 mg/mL was added to the drinking water of 4-week-old apoE-null female mice. Eight weeks later, HDL cholesterol levels and apoA-I levels were markedly increased in the mice that received DMPC. HDL function was also dramatically improved in the mice receiving DMPC, and there was a significant reduction in aortic lesions (P=0.021) in the DMPC mice but not in those receiving lecithin. Adding 1.0 mg/mL of DMPC to the drinking water of 10-month-old apoE-null female mice for 5 weeks caused regression of aortic sinus lesions (P=0.003). Adding 1.0 mg/mL DMPC to the drinking water of 6-month-old apoE-null male mice for 8 weeks significantly reduced aortic sinus lesion area (P=0.0031) and en face whole aorta lesion area (P=0.001), whereas adding the same concentrations of soy or egg lecithin did not significantly alter lesion area. Jejunal apoA-I synthesis and plasma apoA-I levels were increased 2- to 3-fold in mice receiving DMPC but not soy or egg lecithin.

Conclusions--DMPC (but not lecithin) raises HDL cholesterol and apoA-I, improves HDL function, and prevents lesions or causes their regression in apoE-null mice.

Key words: atherosclerosis • lipids • lipoproteins

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