Processing of apolipoprotein B-100 of human plasma low density lipoproteins by tissue and plasma kallikreins.

Human plasma low density lipoproteins (LDL) are the major carriers of cholesterol and cholesteryl esters in the circulation. Their increased levels correlate positively with increased risk of coronary artery disease. LDL contain a single major apolipoprotein of apparent molecular weight (Mr) = 550,000, designated apolipoprotein B-100 (apoB-100), and in some LDL preparations, minor components termed apoB-74 (410,000) and apoB-26 (145,000). The structural relationship of the apoB-74 and -26 proteins to the apoB-100 has remained obscure and their roles in cholesterol metabolism are unknown. In the present study, we show that the addition of kaolin to plasma anticoagulated with EDTA induces the proteolytic cleavage of apoB-100. As a result, two apoB peptides are produced with Mr indistinguishable from plasma apoB-74 and -26. The specific cleavage of apoB-100 was mimicked in vitro by purified human plasma and tissue kallikreins. In contrast, thrombin, factor Xa, plasmin, trypsin, and chymotrypsin did not produce these peptides when incubated with LDL. The findings of the study suggest that apoB-74 and -26 are proteolytic fragments of apoB-100 and that the endogenous protease has a kallikrein-like specificity for DLD-apoB-100. The role of plasma and tissue kallikreins in cholesterol metabolism remains to be determined.