Submitted on August 31, 2007
Revised on October 30, 2007
Accepted on November 8, 2007
Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymase
Miriam Lee-Rueckert, Riikka Vikstedt, Jari Metso, Matti Jauhiainen, and Petri T. Kovanen
Wihuri Research Institute, Helsinki FIN-00140
Corresponding Author: petri.kovanen{at}wri.fi
Human atherosclerotic intima contains mast cells that secrete the neutral protease chymase into the intimal fluid, which also contains HDL-modifying proteins, such as cholesteryl ester transfer protein (CETP), in addition to abundant amounts of nascent discoidal HDL particles. Here, we studied chymase-dependent degradation of (a) CETP isolated from human plasma and (b) CETP-HDL complexes, and the functional consequences of such degradations. Incubation with chymase caused a rapid cleavage of CETP protein, yielding a specific proteolytic pattern with a concomitant reduction in its CE transfer activity. These chymase-dependent effects were attenuated after CETP was complexed with HDL. This attenuation was more effective when CETP was complexed with HDL3 and HDL2 than with discoidal rHDL. Conversely, rHDL, but not spherical HDLs, were protected in such CETP complexes against functional inactivation by chymase. Thus, in contrast to the complexes of CETP with spherical HDLs, the ability of the CETP-rHDL complexes to promote cholesterol efflux from macrophage foam cells remained unchanged despite treatment with chymase. In summary, complexation of CETP and HDL modifies their resistance to proteolytic inactivation: spherical HDLs protect CETP, and CETP protects discoidal HDL. The results suggest that in inflamed atherosclerotic intima, CETP, via its complexation with HDL has a novel protective role in early steps of reverse cholesterol transport.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
