Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity
Approximately 12% of patients with acute myocardial infarction (AMI) experience a recurrent major adverse cardiovascular event within 1 year of their primary event, with most occurring within the first 90 days. Thus, there is a need for new therapeutic approaches that address this 90‐day post‐AMI hi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.121.024754 |
| _version_ | 1797301678359183360 |
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| author | Bronwyn A. Kingwell Stephen J. Nicholls Elena Velkoska Svetlana A. Didichenko Danielle Duffy Serge Korjian C. Michael Gibson |
| author_facet | Bronwyn A. Kingwell Stephen J. Nicholls Elena Velkoska Svetlana A. Didichenko Danielle Duffy Serge Korjian C. Michael Gibson |
| author_sort | Bronwyn A. Kingwell |
| collection | DOAJ |
| description | Approximately 12% of patients with acute myocardial infarction (AMI) experience a recurrent major adverse cardiovascular event within 1 year of their primary event, with most occurring within the first 90 days. Thus, there is a need for new therapeutic approaches that address this 90‐day post‐AMI high‐risk period. The formation and eventual rupture of atherosclerotic plaque that leads to AMI is elicited by the accumulation of cholesterol within the arterial intima. Cholesterol efflux, a mechanism by which cholesterol is removed from plaque, is predominantly mediated by apolipoprotein A‐I, which is rapidly lipidated to form high‐density lipoprotein in the circulation and has atheroprotective properties. In this review, we outline how cholesterol efflux dysfunction leads to atherosclerosis and vulnerable plaque formation, including inflammatory cell recruitment, foam cell formation, the development of a lipid/necrotic core, and degradation of the fibrous cap. CSL112, a human plasma‐derived apolipoprotein A‐I, is in phase 3 of clinical development and aims to reduce the risk of recurrent cardiovascular events in patients with AMI in the first 90 days after the index event by increasing cholesterol efflux. We summarize evidence from preclinical and clinical studies suggesting that restoration of cholesterol efflux by CSL112 can stabilize plaque by several anti‐inflammatory/immune‐regulatory processes. These effects occur rapidly and could stabilize vulnerable plaques in patients who have recently experienced an AMI, thereby reducing the risk of recurrent major adverse cardiovascular events in the high‐risk early post‐AMI period. |
| first_indexed | 2024-03-07T23:26:01Z |
| format | Article |
| id | doaj.art-b3632ad952644828a192fd9015e426e9 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-07T23:26:01Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-b3632ad952644828a192fd9015e426e92024-02-21T04:32:43ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-04-0111810.1161/JAHA.121.024754Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux CapacityBronwyn A. Kingwell0Stephen J. Nicholls1Elena Velkoska2Svetlana A. Didichenko3Danielle Duffy4Serge Korjian5C. Michael Gibson6CSL LimitedBio21 Institute Melbourne Victoria AustraliaVictorian Heart InstituteMonash University Clayton Victoria AustraliaCSL LimitedBio21 Institute Melbourne Victoria AustraliaCSL Behring AG, Research and Development Bern SwitzerlandCSL Behring King of Prussia PAPERFUSE Study Group, Cardiovascular Division Departments of Medicine Beth Israel Deaconess Medical CenterHarvard Medical School Boston MAPERFUSE Study Group, Cardiovascular Division Departments of Medicine Beth Israel Deaconess Medical CenterHarvard Medical School Boston MAApproximately 12% of patients with acute myocardial infarction (AMI) experience a recurrent major adverse cardiovascular event within 1 year of their primary event, with most occurring within the first 90 days. Thus, there is a need for new therapeutic approaches that address this 90‐day post‐AMI high‐risk period. The formation and eventual rupture of atherosclerotic plaque that leads to AMI is elicited by the accumulation of cholesterol within the arterial intima. Cholesterol efflux, a mechanism by which cholesterol is removed from plaque, is predominantly mediated by apolipoprotein A‐I, which is rapidly lipidated to form high‐density lipoprotein in the circulation and has atheroprotective properties. In this review, we outline how cholesterol efflux dysfunction leads to atherosclerosis and vulnerable plaque formation, including inflammatory cell recruitment, foam cell formation, the development of a lipid/necrotic core, and degradation of the fibrous cap. CSL112, a human plasma‐derived apolipoprotein A‐I, is in phase 3 of clinical development and aims to reduce the risk of recurrent cardiovascular events in patients with AMI in the first 90 days after the index event by increasing cholesterol efflux. We summarize evidence from preclinical and clinical studies suggesting that restoration of cholesterol efflux by CSL112 can stabilize plaque by several anti‐inflammatory/immune‐regulatory processes. These effects occur rapidly and could stabilize vulnerable plaques in patients who have recently experienced an AMI, thereby reducing the risk of recurrent major adverse cardiovascular events in the high‐risk early post‐AMI period.https://www.ahajournals.org/doi/10.1161/JAHA.121.024754acute myocardial infarctionapolipoprotein A‐Iatherosclerotic plaquecholesterol efflux |
| spellingShingle | Bronwyn A. Kingwell Stephen J. Nicholls Elena Velkoska Svetlana A. Didichenko Danielle Duffy Serge Korjian C. Michael Gibson Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease acute myocardial infarction apolipoprotein A‐I atherosclerotic plaque cholesterol efflux |
| title | Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity |
| title_full | Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity |
| title_fullStr | Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity |
| title_full_unstemmed | Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity |
| title_short | Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity |
| title_sort | antiatherosclerotic effects of csl112 mediated by enhanced cholesterol efflux capacity |
| topic | acute myocardial infarction apolipoprotein A‐I atherosclerotic plaque cholesterol efflux |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.121.024754 |
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