Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality
Background Complement activation may promote atherosclerosis. Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce. Methods and Results...
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2025-02-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.038316 |
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| author | Mieke C. Louwe Chrysostomi Gialeli Annika E. Michelsen Sverre Holm Andreas Edsfeldt Karolina Skagen Tove Lekva Maria Belland Olsen Vigdis Bjerkeli Therese Schjørlien Kristine Stø Xiang Yi Kong Tuva B. Dahl Per H. Nilsson Peter Libby Pål Aukrust Tom Eirik Mollnes Thor Ueland Mona Skjelland Isabel Gonçalves Bente Halvorsen |
| author_facet | Mieke C. Louwe Chrysostomi Gialeli Annika E. Michelsen Sverre Holm Andreas Edsfeldt Karolina Skagen Tove Lekva Maria Belland Olsen Vigdis Bjerkeli Therese Schjørlien Kristine Stø Xiang Yi Kong Tuva B. Dahl Per H. Nilsson Peter Libby Pål Aukrust Tom Eirik Mollnes Thor Ueland Mona Skjelland Isabel Gonçalves Bente Halvorsen |
| author_sort | Mieke C. Louwe |
| collection | DOAJ |
| description | Background Complement activation may promote atherosclerosis. Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce. Methods and Results We measured, by ELISA, plasma levels of factor D, properdin, C3bBbP (C3 convertase), and factor H in patients with advanced carotid atherosclerosis in a Discovery (n=324) and in a Validation (n=206) cohort in relation to adverse outcome (mean follow‐up 7.8 and 6.6 years, respectively). Our major findings were as follows. Compared with healthy controls, patients with carotid atherosclerosis had increased plasma levels of factor D, properdin, and C3bBbP (P<0.001), but not factor H, an inhibitor of the alternative complement pathway, compared with controls. Although patients with carotid atherosclerosis had elevated levels of properdin compared with controls, within these patients, low plasma levels of properdin (ie, <median levels of properdin in the patient group) were significantly associated with cardiovascular mortality. This was seen in both the Discovery (HR 2.31, P=0.019) and the Validation cohort (hazard ratio [HR], 2.81, P=0.014). In contrast to the low circulating levels, high intraplaque properdin levels (assessed by ELISA) correlated with markers of plaque vulnerability and symptomatology. Conclusions We show a strong and independent association of low plasma properdin levels with cardiovascular mortality in 2 cohorts. Conversely, the plaque properdin levels linked to features of plaque vulnerability, potentially reflecting increased deposition at the site of inflammation or local production of properdin in the atherosclerotic lesion indicating local enhanced alternative complement pathway activation. |
| format | Article |
| id | doaj-art-633c7c24536b4469a0453abcd3b64b3a |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-633c7c24536b4469a0453abcd3b64b3a2025-02-04T11:00:01ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-02-0114310.1161/JAHA.124.038316Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular MortalityMieke C. Louwe0Chrysostomi Gialeli1Annika E. Michelsen2Sverre Holm3Andreas Edsfeldt4Karolina Skagen5Tove Lekva6Maria Belland Olsen7Vigdis Bjerkeli8Therese Schjørlien9Kristine Stø10Xiang Yi Kong11Tuva B. Dahl12Per H. Nilsson13Peter Libby14Pål Aukrust15Tom Eirik Mollnes16Thor Ueland17Mona Skjelland18Isabel Gonçalves19Bente Halvorsen20Research Institute of Internal Medicine, Oslo University Hospital Oslo NorwayDepartment of Clinical Sciences Malmö Lund University Lund SwedenResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayDepartment of Clinical Sciences Malmö Lund University Lund SwedenInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo NorwayResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo NorwayInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo NorwayResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayDepartment of Immunology Oslo University Hospital Rikshospitalet and University of Oslo NorwayDivision of Cardiovascular Medicine Brigham and Women’s Hospital, Harvard Medical School Boston MA USAResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayDepartment of Immunology Oslo University Hospital Rikshospitalet and University of Oslo NorwayResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo NorwayDepartment of Clinical Sciences Malmö Lund University Lund SwedenResearch Institute of Internal Medicine, Oslo University Hospital Oslo NorwayBackground Complement activation may promote atherosclerosis. Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce. Methods and Results We measured, by ELISA, plasma levels of factor D, properdin, C3bBbP (C3 convertase), and factor H in patients with advanced carotid atherosclerosis in a Discovery (n=324) and in a Validation (n=206) cohort in relation to adverse outcome (mean follow‐up 7.8 and 6.6 years, respectively). Our major findings were as follows. Compared with healthy controls, patients with carotid atherosclerosis had increased plasma levels of factor D, properdin, and C3bBbP (P<0.001), but not factor H, an inhibitor of the alternative complement pathway, compared with controls. Although patients with carotid atherosclerosis had elevated levels of properdin compared with controls, within these patients, low plasma levels of properdin (ie, <median levels of properdin in the patient group) were significantly associated with cardiovascular mortality. This was seen in both the Discovery (HR 2.31, P=0.019) and the Validation cohort (hazard ratio [HR], 2.81, P=0.014). In contrast to the low circulating levels, high intraplaque properdin levels (assessed by ELISA) correlated with markers of plaque vulnerability and symptomatology. Conclusions We show a strong and independent association of low plasma properdin levels with cardiovascular mortality in 2 cohorts. Conversely, the plaque properdin levels linked to features of plaque vulnerability, potentially reflecting increased deposition at the site of inflammation or local production of properdin in the atherosclerotic lesion indicating local enhanced alternative complement pathway activation.https://www.ahajournals.org/doi/10.1161/JAHA.124.038316alternative complement pathwaycarotid atherosclerosiscomplementplaque vulnerabilityproperdinstroke |
| spellingShingle | Mieke C. Louwe Chrysostomi Gialeli Annika E. Michelsen Sverre Holm Andreas Edsfeldt Karolina Skagen Tove Lekva Maria Belland Olsen Vigdis Bjerkeli Therese Schjørlien Kristine Stø Xiang Yi Kong Tuva B. Dahl Per H. Nilsson Peter Libby Pål Aukrust Tom Eirik Mollnes Thor Ueland Mona Skjelland Isabel Gonçalves Bente Halvorsen Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease alternative complement pathway carotid atherosclerosis complement plaque vulnerability properdin stroke |
| title | Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality |
| title_full | Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality |
| title_fullStr | Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality |
| title_full_unstemmed | Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality |
| title_short | Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality |
| title_sort | alternative complement pathway in carotid atherosclerosis low plasma properdin levels associate with long term cardiovascular mortality |
| topic | alternative complement pathway carotid atherosclerosis complement plaque vulnerability properdin stroke |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.038316 |
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