Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymase
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 chyma...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2008-02-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520428561 |
| _version_ | 1818930824738766848 |
|---|---|
| author | Miriam Lee-Rueckert Riikka Vikstedt Jari Metso Matti Jauhiainen Petri T. Kovanen |
| author_facet | Miriam Lee-Rueckert Riikka Vikstedt Jari Metso Matti Jauhiainen Petri T. Kovanen |
| author_sort | Miriam Lee-Rueckert |
| collection | DOAJ |
| description | 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 as well as the functional consequences of such degradations. Incubation with chymase caused a rapid cleavage of CETP, yielding a specific proteolytic pattern with a concomitant reduction in its cholesteryl ester 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 reconstituted high density lipoprotein (rHDL). Conversely, rHDL, but not spherical HDLs, was 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. These 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. |
| first_indexed | 2024-12-20T04:06:50Z |
| format | Article |
| id | doaj.art-641d42ac74ad47b9a7d0f9ced6759b88 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T04:06:50Z |
| publishDate | 2008-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-641d42ac74ad47b9a7d0f9ced6759b882022-12-21T19:54:00ZengElsevierJournal of Lipid Research0022-22752008-02-01492358368Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymaseMiriam Lee-Rueckert0Riikka Vikstedt1Jari Metso2Matti Jauhiainen3Petri T. Kovanen4Wihuri Research Institute, Helsinki, FinlandNational Public Health Institute, Department of Molecular Medicine, Biomedicum, Helsinki, FinlandNational Public Health Institute, Department of Molecular Medicine, Biomedicum, Helsinki, FinlandNational Public Health Institute, Department of Molecular Medicine, Biomedicum, Helsinki, FinlandWihuri Research Institute, Helsinki, FinlandHuman 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 as well as the functional consequences of such degradations. Incubation with chymase caused a rapid cleavage of CETP, yielding a specific proteolytic pattern with a concomitant reduction in its cholesteryl ester 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 reconstituted high density lipoprotein (rHDL). Conversely, rHDL, but not spherical HDLs, was 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. These 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.http://www.sciencedirect.com/science/article/pii/S0022227520428561proteolysischolesterol effluxreverse cholesterol transporthigh density lipoprotein |
| spellingShingle | Miriam Lee-Rueckert Riikka Vikstedt Jari Metso Matti Jauhiainen Petri T. Kovanen Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymase Journal of Lipid Research proteolysis cholesterol efflux reverse cholesterol transport high density lipoprotein |
| title | Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymase |
| title_full | Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymase |
| title_fullStr | Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymase |
| title_full_unstemmed | Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymase |
| title_short | Association of cholesteryl ester transfer protein with HDL particles reduces its proteolytic inactivation by mast cell chymase |
| title_sort | association of cholesteryl ester transfer protein with hdl particles reduces its proteolytic inactivation by mast cell chymase |
| topic | proteolysis cholesterol efflux reverse cholesterol transport high density lipoprotein |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520428561 |
| work_keys_str_mv | AT miriamleerueckert associationofcholesterylestertransferproteinwithhdlparticlesreducesitsproteolyticinactivationbymastcellchymase AT riikkavikstedt associationofcholesterylestertransferproteinwithhdlparticlesreducesitsproteolyticinactivationbymastcellchymase AT jarimetso associationofcholesterylestertransferproteinwithhdlparticlesreducesitsproteolyticinactivationbymastcellchymase AT mattijauhiainen associationofcholesterylestertransferproteinwithhdlparticlesreducesitsproteolyticinactivationbymastcellchymase AT petritkovanen associationofcholesterylestertransferproteinwithhdlparticlesreducesitsproteolyticinactivationbymastcellchymase |