(Circulation. 1999;100:1151-1153.)
© 1999 American Heart Association, Inc.
Editorials |
Lipoprotein(a) Concentration and Apolipoprotein(a) Size
A Synergistic Role in Advanced Atherosclerosis?
From the Department of Medicine, University of Washington, Seattle (S.M.M.), and Department of Biochemistry, Queen's University, Kingston, Ontario, Canada (M.L.K.).
Correspondence to Dr Santica Marcovina, Department of Medicine, University of Washington, Box 358750, Seattle, WA 98195-8750. E-mail smm@u.washington.edu
Key Words: Editorials • lipoproteins • apolipoproteins • atherosclerosis
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Introduction |
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Despite more than 3 decades of intense scientific research that has fostered our understanding of the structure and biochemistry of lipoprotein(a) [Lp(a)], the physiopathological role of Lp(a) is still poorly understood. Consequently, despite its recognition as a risk factor for coronary artery disease (CAD), the role of Lp(a) in atherogenesis and the extent to which Lp(a) levels should be assessed in clinical practice remain controversial. Lp(a), which is the most complex and polymorphic of the lipoprotein particles, is formed by an LDL moiety and a unique protein, apo(a), linked to apolipoprotein (apo) B-100 of LDL.1 The most intriguing feature of apo(a) is that it shares an extensive structural homology with plasminogen, a key proenzyme of the fibrinolytic cascade. Kringle V and the protease domains of apo(a) share >85% amino-acid identity with the corresponding plasminogen domains, even though the protease domain of apo(a) does not appear to have a catalytic function. Apo(a) contains 10 different types of a sequence with variable degrees of homology with plasminogen kringle IV. The number of kringle IV type 2 repeats, which is encoded by a varying number of copies in the apo(a) gene,2 varies both within and among individuals, and at least 35 apo(a) size isoforms have been detected in human plasma.3 Despite the presence of LDL, apo(a) imparts to Lp(a) unique properties with respect to synthesis and catabolism. In fact, apo B-100 in Lp(a) particles does not appear to mediate the catabolism of this lipoprotein via the LDL receptor, thus suggesting that the attachment
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