Role of LCAT in HDL remodeling: Investigation of LCAT deficiency states

Bela F. Asztalos, Ernst J. Schaefer, Katalin V. Horvath, Shizuya Yamashita, Michael Miller, Guido Franceschini, and Laura Calabresi

Lipid Metabolism, JM/HNRCA at Tufts Univaresity, Boston, MA 02111

Corresponding Author: bela.asztalos{at}tufts.edu

Objective: To better understand the role of LCAT in HDL metabolism, we compared HDL subpopulations in subjects with homozygous (n=11) and heterozygous (n=11) LCAT deficiency with controls (n=22). Distribution and concentrations of apolipoprotein (apo) A-I-, A-II-, A-IV-, C-I-, C-III-, and E-containing HDL subpopulations were assessed. Results: Compared to controls, homozygotes and heterozygotes had lower LCAT masses (-77% and -13%), and LCAT activities (-99% and -39%), respectively. In homozygotes, the majority of apoA-I was found in small, discoidal, poorly-lipidated preß-1 and a-4 HDL particles with some apoA-I being found in larger, probably stacked, lipid-poor, discoidal HDL particles with a-mobility. No apoC-I-containing HDL was noted and all apoA-II and apoC-III were detected in lipid-poor, preß-mobility particles. ApoE-containing particles were more disperse than normal. Apo-A-IV-containing particles were normal. Heterozygotes had profiles similar to controls, except that apoC-III was only found in small particles with preß-mobility. Conclusions: Our data are consistent with the concepts that LCAT activity: 1) is essential for developing large, spherical, apoA-I-containing HDL and for the formation of normal-sized apoC-I and apoC-III HDL, and 2) has little affect on the conversion of preß-1 into a-4 HDL, only slight effects on apoE HDL, and no effect on apoA-IV HDL particles.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

M. J. Thomas, S. Bhat, and M. G. Sorci-Thomas
Three-dimensional models of HDL apoA-I: implications for its assembly and function
J. Lipid Res., September 1, 2008; 49(9): 1875 - 1883.
[Abstract] [Full Text] [PDF]

S. Lamon-Fava, D. M. Herrington, D. M. Reboussin, M. Sherman, K. V. Horvath, L. A. Cupples, C. White, S. Demissie, E. J. Schaefer, and B. F. Asztalos
Plasma Levels of HDL Subpopulations and Remnant Lipoproteins Predict the Extent of Angiographically-Defined Coronary Artery Disease in Postmenopausal Women
Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 575 - 579.
[Abstract] [Full Text] [PDF]

R. D. Santos, E. J. Schaefer, B. F. Asztalos, E. Polisecki, J. Wang, R. A. Hegele, L. R. C. Martinez, M. H. Miname, C. E. Rochitte, P. L. Da Luz, et al.
Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency
J. Lipid Res., February 1, 2008; 49(2): 349 - 357.
[Abstract] [Full Text] [PDF]

All ASBMB Journals	Journal of Biological Chemistry
Molecular and Cellular Proteomics	ASBMB Today

				S. Lamon-Fava, D. M. Herrington, D. M. Reboussin, M. Sherman, K. V. Horvath, L. A. Cupples, C. White, S. Demissie, E. J. Schaefer, and B. F. Asztalos Plasma Levels of HDL Subpopulations and Remnant Lipoproteins Predict the Extent of Angiographically-Defined Coronary Artery Disease in Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 575 - 579. [Abstract] [Full Text] [PDF]

				R. D. Santos, E. J. Schaefer, B. F. Asztalos, E. Polisecki, J. Wang, R. A. Hegele, L. R. C. Martinez, M. H. Miname, C. E. Rochitte, P. L. Da Luz, et al. Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency J. Lipid Res., February 1, 2008; 49(2): 349 - 357. [Abstract] [Full Text] [PDF]