The inter-relation of fibrin, lipoprotein(a) and plasminogen in human atherosclerotic lesions.
The low density lipoprotein (LDL) variant, lipoprotein(a) (Lp(a)) is a risk factor for coronary heart disease, and in this study we have examined its interaction with the arterial wall. Samples of normal intima and atherosclerotic lesions were extracted with buffer containing EDTA and protease inhibitors and assayed for LDL and Lp(a) by radial immunodiffusion. The extract tissues were washed, then incubated with plasmin and the amounts of LDL and Lp(a) released into the digest were measured. Intimal Lp(a) concentrations were compared to Lp(a) in the patients' blood. Levels of both soluble and plasmin-releasable Lp(a) were related to type of intimal sample and blood Lp(a) level. In early proliferative lesions there was a significant correlation between plasmin-releasable Lp(a) and blood Lp(a) (r = 0.631, P less than 0.002). Highest levels of plasmin-releasable Lp(a) were found in more advanced lesions that had accumulated some lipid. In extracts the amounts of LDL were 5-20 fold greater than Lp(a) but in the plasmin digests Lp(a) could account for most of the apoB detected, suggesting that Lp(a) may bind to fibrin in the lesion through its plasminogen-like structures and thus contribute to lipid accumulation in fibrous plaques. Plasminogen cannot be detected by rocket immunoelectrophoresis in samples from about two-thirds of aortas, and it seemed possible that the large plasminogen-like apo(a) component of Lp(a) was interfering with intimal uptake or retention of plasminogen, or its immunoassay. However, in 28 samples of intima or thrombi from 16 patients there was no relation between amounts of Lp(a) and plasminogen.
Smith
E B
EB
Department of Clinical Biochemistry, Aberdeen Royal Infirmary, Foresterhill, UK.
Crosbie
L
L
Cochran
S
S
D001011:Aorta / Q000737:chemistry*; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D001665:Binding Sites; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology
D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D005337:Fibrin; D010958:Plasminogen