Plasminogen kringle types

Lipoprotein (a) is an independent risk factor for coronary artery disease [68]. It consists of two components an LDL particle and apolipoprotein (a) which are linked by a disulfide bridge. Apo(a) reveals a genetically determined size polymorphism, resulting from a variable number of plasminogen kringle IV-type repeats [69]. Statins either do not affect Lp(a) or may even increase Lp(a) [70, 71]. In a study of 51 FH patients, treated with 40 mgd 1 pravastatin, it has been shown that the increase in Lp(a) was greatest in patients with the low molecular-weight apo(a) phenotypes [70]. 

CHAPTER 36, FIGURE 5 Motif structures within coagulation proteins. Common motifs are found in the amino terminal regions of the proteinase precursor molecules. Shown are the kringle motifs and EGF-like motifs found in the vitamin K-dependent proteins and in plasminogen. Fibronectin (types I and II) motifs and apple motifs (named from their two-dimensional representations) are also present but not shown. Some epidermal growth factor-like domains contain P-hydroxylated Asp residues. The cartoon structures for the motifs are derived from three-dimensional structures determined by x-ray crystallography or by two-dimensional NMR spectroscopy. 

The heterogeneity of Lp(a) is related to ultrastructural motifs in the molecule, strongly resembling the so-called kringles found in both plasminogen and other plasma proteins, such as proteases of the coagulation system (tissue type plasminogen activator and prothrombin) (Fig. 2). 

The evolutionary hypothesis is that the ancestral molecule of apo(a) was a plasminogen-type protein, having five kringles, that emerged by a duplication event from a protein with one kringle and one serine protease domain about 300 million years ago (12). 

Wl. Wagner, O. F., de Vries, C., Hohmann, C., Veerman, H., and Pannekoek, H., Interaction between plasminogen activator inhibitor-1 (PAI-1) bound to fibrin and either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) Binding of t-PA/PAI-1 complexes to fibrin mediated by both the finger and kringle-2 domain of t-PA. J. Clin. Invest. 84, 647-655 (1989). 

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