Skip to main content
SpringerLink
Log in

Association of lecithin–cholesterol acyltransferase activity measured as a serum cholesterol esterification rate and low-density lipoprotein heterogeneity with cardiovascular risk: a cross-sectional study

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

The cholesterol-esterifying enzyme, lecithin–cholesterol acyltransferase (LCAT), is believed to play a key role in reverse cholesterol transport. However, recent investigations have demonstrated that higher LCAT activity levels increase the formation of triglyceride (TG)-rich lipoproteins (TRLs) and atherogenesis. We hypothesized that higher LCAT activity measured as a serum cholesterol esterification rate by the endogenous substrate method might increase the formation of TRLs and thereby alter low-density lipoprotein (LDL) heterogeneity. The estimated LDL particle size [relative LDL migration (LDL-Rm)] was measured by polyacrylamide gel electrophoresis with the LipoPhor system (Joko, Tokyo, Japan) in 538 consecutive patients with at least risk factor for atherosclerosis. Multivariate regression analysis after adjustments for traditional risk factors identified elevated TRL-related marker (TG, remnant-like particle cholesterol, apolipoprotein C-II, and apolipoprotein C-III) levels as independent predictors of smaller-sized LDL particle size, both in the overall subject population and in the subset of patients with serum LDL cholesterol levels of <100 mg/dL. Area under the receiver operating characteristic curve of the LCAT activity (0.79; sensitivity 60 %; specificity 84.8 %) was observed for the evaluation of the indicators of an LDL-Rm value of ≥0.40, which suggests the presence of large amounts of small-dense LDL. The results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in LDL particle size. Therefore, to reduce the risk of atherosclerotic cardiovascular disease, it may be of importance to pay attention not only to a quantitative change in the serum LDL-C, but also to the LCAT activity which is possibly associated with LDL heterogeneity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Glomset JA (1968) The plasma lecithins:cholesterol acyltransferase reaction. J Lipid Res 9:155–167

    CAS  PubMed  Google Scholar 

  2. Ng DS (2012) The role of lecithin:cholesterol acyltransferase in the modulation of cardiometabolic risks—a clinical update and emerging insights from animal models. Biochim Biophys Acta 1821:654–659

    Article  CAS  PubMed  Google Scholar 

  3. Calabresi L, Simonelli S, Gomaraschi M, Franceschini G (2012) Genetic lecithin:cholesterol acyltransferase deficiency and cardiovascular disease. Atherosclerosis 222:299–306

    Article  CAS  PubMed  Google Scholar 

  4. Solaji-Bozicevi N, Stavljeni-Rukavina A, Sesto M (1994) Lecithin-cholesterol acyltransferase activity in patients with coronary artery disease examined by coronary angiography. Clin Investig 72:951–956

    Article  Google Scholar 

  5. Sethi AA, Sampson M, Warnick R, Muniz N, Vaisman B, Nordestgaard BG, Tybjaerg-Hansen A, Remaley AT (2010) High pre-beta1 HDL concentrations and low lecithin:cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol. Clin Chem 56:1128–1137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Holleboom AG, Kuivenhoven JA, Vergeer M, Hovingh GK, van Miert JN, Wareham NJ, Kastelein JJ, Khaw KT, Boekholdt SM (2010) Plasma levels of lecithin:cholesterol acyltransferase and risk of future coronary artery disease in apparently healthy men and women: a prospective case–control analysis nested in the EPIC-Norfolk population study. J Lipid Res 51:416–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dullaart RP, Perton F, van der Klauw MM, Hillege HL, Sluiter WJ, PREVEND Study Group (2010) High plasma lecithin:cholesterol acyltransferase activity does not predict low incidence of cardiovascular events: possible attenuation of cardioprotection associated with high HDL cholesterol. Atherosclerosis 208:537–542

    Article  CAS  PubMed  Google Scholar 

  8. Dullaart RP, Tietge UJ, Kwakernaak AJ, Dikkeschei BD, Perton F, Tio RA (2014) Alterations in plasma lecithin:cholesterol acyltransferase and myeloperoxidase in acute myocardial infarction: implications for cardiac outcome. Atherosclerosis 234:185–192

    Article  CAS  PubMed  Google Scholar 

  9. Dullaart RP, Perton F, Kappelle PJ, de Vries R, Sluiter WJ, van Tol A (2010) Plasma lecithin:cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men. Biochim Biophys Acta 1801:84–88

    Article  CAS  PubMed  Google Scholar 

  10. Calabresi L, Baldassarre D, Simonelli S, Gomaraschi M, Amato M, Castelnuovo S, Frigerio B, Ravani A, Sansaro D, Kauhanen J, Rauramaa R, de Faire U, Hamsten A, Smit AJ, Mannarino E, Humphries SE, Giral P, Veglia F, Sirtori CR, Franceschini G, Tremoli E (2011) Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk. J Lipid Res 52:1569–1574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dullaart RP, Perton F, Sluiter WJ, de Vries R, van Tol A (2008) Plasma lecithin:cholesterol acyltransferase activity is elevated in metabolic syndrome and is an independent marker of increased carotid artery intima media thickness. J Clin Endocrinol Metab 93:4860–4866

    Article  CAS  PubMed  Google Scholar 

  12. Tanaka S, Yasuda T, Ishida T, Fujioka Y, Tsujino T, Miki T, Hirata K (2013) Increased serum cholesterol esterification rates predict coronary heart disease and sudden death in a general population. Arterioscler Thromb Vasc Biol 33:1098–1104

    Article  CAS  PubMed  Google Scholar 

  13. Murakami T, Michelagnoli S, Longhi R, Gianfranceschi G, Pazzucconi F, Calabresi L, Sirtori CR, Franceschini G (1995) Triglycerides are major determinants of cholesterol esterification/transfer and HDL remodeling in human plasma. Arterioscler Thromb Vasc Biol 15:1819–1828

    Article  CAS  PubMed  Google Scholar 

  14. Sutherland WH, Temple WA, Nye ER, Herbison PG (1979) Lecithin:cholesterol acyltransferase activity, plasma and lipoprotein lipids and obesity in men and women. Atherosclerosis 34:319–327

    Article  CAS  PubMed  Google Scholar 

  15. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S, American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease (2011) Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation 123:2292–2333

    Article  PubMed  Google Scholar 

  16. Takagi H, Niwa M, Mizuno Y, Yamamoto H, Goto SN, Umemoto T (2014) Effects of rosuvastatin versus atorvastatin on small dense low-density lipoprotein: a meta-analysis of randomized trials. Heart Vessels 29:287–299

    Article  PubMed  Google Scholar 

  17. Nagasaki T, Akanuma Y (1977) A new colorimetric method for the determination of plasma lecithin-cholesterol acyltransferase activity. Clin Chim Acta 75:371–375

    Article  CAS  PubMed  Google Scholar 

  18. Bartholome M, Niedmann D, Wieland H, Seidel D (1981) An optimized method for measuring lecithin : Cholesterol acyltransferase activity, independent of the concentration and quality of the physiological substrate. Biochim Biophys Acta 664:327–334

    Article  CAS  PubMed  Google Scholar 

  19. Kobori K, Saito K, Ito S, Kotani K, Manabe M, Kanno T (2002) A new enzyme-linked immunosorbent assay with two monoclonal antibodies to specific epitopes measure human lecithin-cholesterol acyltransferase. J Lipid Res 43:325–334

    CAS  PubMed  Google Scholar 

  20. DeLong DM, DeLong ER, Wood PD, Lippel K, Rifkind BM (1986) A comparison of methods for the estimation of plasma low- and very low-density lipoprotein cholesterol. The Lipid Research Clinics Prevalence Study. JAMA 256:2372–2377

    Article  CAS  PubMed  Google Scholar 

  21. Hirano T, Ito Y, Yoshino G (2005) Measurement of small dense low-density lipoprotein particles. J Atheroscler Thromb 12:67–72

    Article  CAS  PubMed  Google Scholar 

  22. Tani S, Matsumoto M, Nagao K, Hirayama A (2014) Association of triglyceride-rich lipoproteins-related markers and low-density lipoprotein heterogeneity with cardiovascular risk: effectiveness of polyacrylamide-gel electrophoresis as a method of determining low-density lipoprotein particle size. J Cardiol 63:60–68

    Article  PubMed  Google Scholar 

  23. Eržen B, Šabovič M (2013) In young post-myocardial infarction male patients elevated plasminogen activator inhibitor-1 correlates with insulin resistance and endothelial dysfunction. Heart Vessels 28:570–577

    Article  PubMed  Google Scholar 

  24. Hopkins GJ, Barter PJ (1983) Role of esterified cholesterol transfers in the regulation of plasma cholesterol esterification. Atherosclerosis 49:177–185

    Article  CAS  PubMed  Google Scholar 

  25. Chen CH, Albers JJ (1982) Distribution of lecithin-cholesterol acyltransferase (LCAT) in human plasma lipoprotein fractions. Evidence for the association of active LCAT with low density lipoproteins. Biochem Biophys Res Commun 107:1091–1096

    Article  CAS  PubMed  Google Scholar 

  26. Vanloo B, Peelman F, Deschuymere K, Taveirne J, Verhee A, Gouyette C, Labeur C, Vandekerckhove J, Tavernier J, Rosseneu M (2000) Relationship between structure and biochemical phenotype of lecithin:cholesterol acyltransferase (LCAT) mutants causing fish-eye disease. J Lipid Res 41:752–761

    CAS  PubMed  Google Scholar 

  27. Fielding CJ, Fielding PE (1981) Regulation of human plasma lecithin:cholesterol acyltransferase activity by lipoprotein acceptor cholesteryl ester content. J Biol Chem 256:2102–2104

    CAS  PubMed  Google Scholar 

  28. Chung BH, Segrest JP, Franklin F (1998) In vitro production of beta-very low density lipoproteins and small, dense low density lipoproteins in mildly hypertriglyceridemic plasma: role of activities of lecithin: cholesterol acyltransferase, cholesteryl ester transfer proteins and lipoprotein lipase. Atherosclerosis 141(2):209–225

    Article  CAS  PubMed  Google Scholar 

  29. Albers JJ, Chen CH, Adolphson J (1981) Lecithin:cholesterol acyltransferase (LCAT) mass; its relationship to LCAT activity and cholesterol esterification rate. J Lipid Res 22:1206–1213

    CAS  PubMed  Google Scholar 

  30. Dobiásová M, Frohlich J (1998) Understanding the mechanism of LCAT reaction may help to explain the high predictive value of LDL/HDL cholesterol ratio. Physiol Res 47:387–397

    PubMed  Google Scholar 

  31. Dobiasova M, Stribrna J, Sparks DL, Pritchard PH, Frohlich JJ (1991) Cholesterol esterification rates in very low density lipoprotein- and low density lipoprotein-depleted plasma. Relation to high density lipoprotein subspecies, sex, hyperlipidemia, and coronary artery disease. Arterioscler Thromb 11:64–70

    Article  CAS  PubMed  Google Scholar 

  32. Gylling H, Miettinen TA (1992) Non-cholesterol sterols, absorption and synthesis of cholesterol and apolipoprotein A-I kinetics in a Finnish lecithin-cholesterol acyltransferase deficient family. Atherosclerosis 95:25–33

    Article  CAS  PubMed  Google Scholar 

  33. Ng DS, Xie C, Maguire GF, Zhu X, Ugwu F, Lam E, Connelly PW (2004) Hypertriglyceridemia in lecithin-cholesterol acyltransferase-deficient mice is associated with hepatic overproduction of triglycerides, increased lipogenesis, and improved glucose tolerance. J Biol Chem 279:7636–7642

    Article  CAS  PubMed  Google Scholar 

  34. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E, Investigators PROVEIT-TIMI (2008) Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 51:724–730

    Article  CAS  PubMed  Google Scholar 

  35. Faergeman O, Holme I, Fayyad R, Bhatia S, Grundy SM, Kastelein JJ, LaRosa JC, Larsen ML, Lindahl C, Olsson AG, Tikkanen MJ, Waters DD, Pedersen TR, Steering Committees of IDEAL and TNT Trials (2009) Plasma triglycerides and cardiovascular events in the treating to new targets and incremental decrease in end-points through aggressive lipid lowering trials of statins in patients with coronary artery disease. Am J Cardiol 104:459–463

    Article  CAS  PubMed  Google Scholar 

  36. Francone OL, Gurakar A, Fielding C (1989) Distribution and functions of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in plasma lipoproteins. Evidence for a functional unit containing these activities together with apolipoproteins A-I and D that catalyzes the esterification and transfer of cell-derived cholesterol. J Biol Chem 264:7066–7072

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was presented at the 27th Annual Meeting of Japanese Coronary Association, Symposium 1, 2013, Kumamoto, Japan.

Conflict of interest

All the authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Health Planning Center, Nihon University Hospital, 1-6 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8309, Japan

    Shigemasa Tani & Atsuhiko Takahashi

  2. Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

    Shigemasa Tani, Atsuhiko Takahashi, Ken Nagao & Atsushi Hirayama

Authors
  1. Shigemasa Tani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atsuhiko Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ken Nagao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Atsushi Hirayama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shigemasa Tani.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tani, S., Takahashi, A., Nagao, K. et al. Association of lecithin–cholesterol acyltransferase activity measured as a serum cholesterol esterification rate and low-density lipoprotein heterogeneity with cardiovascular risk: a cross-sectional study. Heart Vessels 31, 831–840 (2016). https://doi.org/10.1007/s00380-015-0678-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-015-0678-9

Keywords

Search

Navigation