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Sphingomyelinase Induces Aggregation and Fusion of Small Very Low–Density Lipoprotein and Intermediate-Density Lipoprotein Particles and Increases Their Retention to Human Arterial Proteoglycans

2005; Lippincott Williams & Wilkins; Volume: 25; Issue: 8 Linguagem: Inglês

10.1161/01.atv.0000168912.42941.60

1524-4636

Katariina Öörni, Pirjo Posio, Mika Ala‐Korpela, Matti Jauhiainen, Petri T. Kovanen,

Blood Coagulation and Thrombosis Mechanisms

Objectives— Infiltration of low-density lipoprotein (LDL) into subendothelial space is an early step in atherosclerosis. In addition to LDL particles, small very low–density lipoprotein (sVLDL) and intermediate-density lipoprotein (IDL) particles are also able to enter the arterial intima and be retained within the subendothelial extracellular matrix. Here we compared how proteolysis with α-chymotrypsin and phospholipid hydrolysis with phospholipase A 2 or sphingomyelinase (SMase) of sVLDL, IDL, and LDL particles can influence their aggregation, fusion, and binding to human arterial proteoglycans in vitro. Methods and Results— In each of the 3 lipoprotein classes, the particles became only slightly aggregated with α-chymotrypsin or phospholipase A 2 . However, the particles strongly aggregated when treated with SMase. The aggregated/fused particles were found to bind to proteoglycans in proteoglycan affinity chromatography more tightly than the native-sized counterparts. In addition, in a microtiter well assay, the binding of SMase-treated lipoproteins was enhanced: the amounts of proteoglycan-bound SMase-treated LDL, IDL, and sVLDL were 4-, 5-, and 20-fold higher, respectively, than the amounts of proteoglycan-bound native lipoproteins. Conclusion— These results imply a specific role for SMase as an sVLDL- and IDL-modifying enzyme and also suggest a novel mechanism of lipid accumulation in atherogenesis, namely enhanced retention of atherogenic triglyceride-rich lipoprotein particles in intimal areas expressing extracellular SMase activity.