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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1678.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Katariina Öörni; Pirjo Posio; Mika Ala-Korpela; Matti Jauhiainen; Petri T. Kovanen

From the Wihuri Research Institute (K.Ö., P.P., M.A.-K., P.T.K.), Helsinki; the Laboratory of Computational Engineering (M.A.-K.), Helsinki University of Technology; and the Department of Molecular Medicine (M.J.), National Public Health Institute, Biomedicum, Helsinki, Finland.

Correspondence to Katariina Öörni, PhD, Wihuri Research Institute Kalliolinnantie 4 FIN-00140, Helsinki, Finland. E-mail kati.oorni{at}wri.fi

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 -chymotrypsin and phospholipid hydrolysis with phospholipase A₂ 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 -chymotrypsin or phospholipase A₂. 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.

Lipolysis of small VLDL and IDL particles by sphingomyelinase induces their aggregation and fusion and enhances binding of the particles to proteoglycans. The results suggest that sphingomyelinase-induced modification of small VLDL and IDL particles can lead to increased retention of the atherogenic triglyceride-rich lipoprotein particles in the arterial intima.

Key Words: VLDL • IDL • proteolysis • lipolysis

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