on May 5, 2005
Published online before print May 5, 2005, doi: 10.1161/01.ATV.0000168912.42941.60
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Submitted on November 7, 2004
Accepted on April 22, 2005
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 *;
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.
* To whom correspondence should be addressed. 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.
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