doi: 10.1161/CIRCRESAHA.108.173146
© 2008 American Heart Association, Inc.
Letters to the Editor |
Is LPL Deficiency Atherogenic?
Okinaka Memorial Institute for Medical Research, Tokyo, Japan, E-mail tetorano{at}gmail.com
To the Editor:
In a recent article in Circulation Research, Zhang et al reported "spontaneous atherosclerosis in aged lipoprotein lipase–deficient mice with severe hypertriglyceridemia on a normal chow diet."1 We would like to draw your attention to differences in lipid metabolism between mice and humans.2,3 Wild-type mice have high levels of serum HDL cholesterol as a result of minimal cholesterol ester transfer protein activity.4 Lipoprotein lipase (LPL)–deficient mice have elevated amounts of cholesterol in the very-low-density lipoprotein fraction. LPL-deficient humans, however, do not have an elevated very-low-density lipoprotein.5 Moreover, LPL-deficient humans have reduced LDL cholesterol levels. Chylomicrons are thought to be nonatherogenic, because they cannot easily enter the arterial wall.6 Although atherogenecity of chylomicrons could be demonstrated in mice, low levels of LDL cholesterol would offset its influence on arteriosclerosis in humans.
Acknowledgments
Sources of Funding
This study was supported in part by a Research Grant from the Takada Science Foundation.
Disclosures
None.
References
1. Zhang X, Qi R, Xian X, Yang F, Blackstein M, Deng X, Fan J, Ross C, Karasinska J, Hayden MR, Liu G. Spontaneous atherosclerosis in aged lipoprotein lipase-deficient mice with severe hypertriglyceridemia on a normal chow diet. Circ Res. 2008; 102: 250–256.
2. Ebara T, Okubo M, Horinishi A, Adachi M, Murase T, Hirano T. No evidence of accelerated atherosclerosis in a 66-yr-old chylomicronemia patient homozygous for the nonsense mutation (Tyr61->stop) in the lipoprotein lipase gene. Atherosclerosis. 2001; 159: 375–379.[CrossRef][Medline] [Order article via Infotrieve]
3. Ebara T, Endo Y, Yoshiike S, Tsuji M, Taguchi S, Murase T, Okubo M. A 60-y-old chylomicronemia patient homozygous for missense mutation (G188E) in the lipoprotein lipase gene showed no accelerated atherosclerosis. Clin Chim Acta. 2007; 386: 100–104.[CrossRef][Medline] [Order article via Infotrieve]
4. Shachter NS, Ebara T, Ramakrishnan R, Steiner G, Breslow JL, Ginsberg HN, Smith JD. Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl. J Clin Invest. 1996; 98: 846–855.[Medline] [Order article via Infotrieve]
5. Previato L, Guardamagna O, Dugi KA, Ronan R, Talley GD, Santamarina-Fojo S, Brewer HB Jr. A novel missense mutation in the C-terminal domain of lipoprotein lipase (Glu410->Val) leads to enzyme inactivation and familial chylomicronemia. J Lipid Res. 1994; 35: 1552–1560.[Abstract]
6. Ebara T, Ramakrishnan R, Steiner G, Shachter NS. Chylomicronemia due to apolipoprotein CIII overexpression in apolipoprotein E-null mice. Apolipoprotein CIII-induced hypertriglyceridemia is not mediated by effects on apolipoprotein E. J Clin Invest. 1997; 99: 2672–2681.[Medline] [Order article via Infotrieve]
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