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(Circulation. 2001;104:2498.)
© 2001 American Heart Association, Inc.

From Bench to Bedside

Exploiting the Vascular Protective Effects of High-Density Lipoprotein and its Apolipoproteins

An Idea Whose Time for Testing Is Coming, Part II

Prediman K. Shah, MD; Sanjay Kaul, MD; Jan Nilsson, MD, PhD; Bojan Cercek, MD, PhD

From the Atherosclerosis Research Center, Division of Cardiology and Burns and Allen research Institute, Department of Medicine, Cedars Sinai Medical Center and UCLA School of Medicine (P.K.S., S.K., B.C.), Los Angeles, Calif, and the University of Malmo, Lund, Sweden (J.N).

Correspondence to P.K. Shah, MD, Director, Division of Cardiology and Atherosclerosis Research Center, Room 5347, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail shahp@cshs.org

Key Words: lipoproteins • atherosclerosis • apolipoproteins

	Introduction

 
Despite the benefits of currently available preventative and therapeutic interventions, atherosclerotic vascular disease continues to be a major cause of morbidity and mortality in much of the Western world. This emphasizes the need for additional preventive and therapeutic interventions exploiting new targets to compliment and augment the results of LDL lowering and other current strategies. One such potential target is HDL and its apolipoproteins. A large body of experimental evidence suggests that augmenting the levels and/or function of HDL and its apolipoproteins can have major vascular protective effects ranging from prevention to stabilization and regression, independent of total or non-HDL cholesterol levels. Therefore, we think that the time is ripe for the development and clinical testing of this new frontier in antiatherogenic strategy. In the present article, we will review the structure/function of HDL and explore means of enhancing the levels and/or function of HDL and its apolipoproteins for vascular protection.

	Structural and Functional Heterogeneity of HDL Particles

 
HDL cholesterol particles consist of an outer amphipathic layer of free cholesterol, phospholipid, and several apolipoproteins (apolipoprotein A-I [the most abundant] and apolipoproteins AII, C, E, AIV, J [clusterin], and D) on the surface, with a triglyceride and cholesterol ester–rich hydrophobic core. Apolipoprotein A-I constitutes 70% and apolipoprotein A-II makes up 20% of the protein content of HDL. Apolipoprotein A-I is synthesized in the liver and intestines in man and mice (and mostly in the intestines in rabbits), whereas apolipoprotein A-II is synthesized mostly in the liver. The gene for apolipoprotein A-I is located on chromosome 11 adjacent to . . . [Full Text of this Article]

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