Lecithin-cholesterol acyltransferase: old friend or foe in atherosclerosis? Sandra Kunnen, Miranda Van Eck Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands Corresponding author: M. Van Eck, Division of Biopharmaceutics, Gorlaeus Laboratories, Einsteinweg 55, 2333 CC Leiden, The Netherlands Tel. +31-71-5276238 Fax. +31-71-5276032 Email:[email protected]Abbreviated title: LCAT: old friend or foe in atherosclerosis? by guest, on May 15, 2018 www.jlr.org Downloaded from
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Lecithin-cholesterol acyltransferase:
old friend or foe in atherosclerosis?
Sandra Kunnen, Miranda Van Eck
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories,
Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands
Corresponding author:
M. Van Eck, Division of Biopharmaceutics, Gorlaeus Laboratories,
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Table 2. LCAT in patients with cardiovascular disease
Study Study design Disease LCAT Atherosclerosis related effect
Activity (nmol/ml/h) Wells, 1986 (104)
Male CVD patients Control No lesion Single vessel Double vessel Triple vessel Myocardial infarction
91 84 126 121 125 80
Increased LCAT in subjects with increased atherosclerosis severity
Pro-atherogenic
Šolajić-Božičević, 1994 (115)
CVD patients No lesion Single vessel Double vessel Triple vessel
107 55 32 16
Reduced LCAT in subjects with increased atherosclerosis severity
Anti-atherogenic
Dullaart, 2010 (116)
PREVEND Inhabitants of the city of Groningen, aged 28-75 years when recruited
Control (men) Case (men)
111 116
High plasma LCAT activity does not predict reduced CVD risk, and may attenuate cardioprotection associated with higher HDL cholesterol.
Possibly pro-atherogenic
Odds ratio for CAD LCAT quartiles Holleboom, 2010 (117)
Men: 1 Women: 1 1
Men: 0.83 Women: 0.88 2 Men: 0.75 Women: 1.14 3
EPIC-NORFOLK Inhabitants of the city of Norfolk, aged 45-74 when recruited
Men: 0.71 Women: 1.35 4
Decreased risk of CAD with increasing LCAT levels in men, while the risk of CAD in women increased with increasing LCAT levels.
Anti-atherogenic in men Pro-atherogenic in women
cIMTmax (mm) Calabresi, 2011 (80)
Men: 1.35 Women: 1.19 1
Men: 1.37 Women: 1.22 2 Men: 1.33 Women: 1.23 3
IMPROVE Subjects with high cardiovascular risk
Men: 1.35 Women: 1.27 4
Low plasma levels of LCAT associated with decreased cIMT in women, but not in men
Pro-atherogenic in women, but not in men
CVD: Cardiovascular Disease; CAD: Coronary Artery Disease; PREVEND: Prevention of renal and vascular end-stage disease study of 40,856 inhabitants (age range 28-75 years) of the city of Groningen in The
Netherlands; EPIC-NORFOLK: European Prospective Investigation into Cancer and Nutrition of over 30,000 inhabitants (age range 45-74 years) of the city of Norfolk in England; IMPROVE: A prospective, multicentre,
longitudinal, observational study of 3711 subjects (age range 54–79 years) with at least three vascular risk factors recruited in seven centres in Finland, France, Italy, the Netherlands, and Sweden.
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