Yosta Vegting , Katie ML. Hanford , Aldo Jongejan , Gayle RS. Gajadin , Miranda Versloot , Nelly D. van der Bom-Baylon , Tamara Dekker , E. Lars Penne , Joost W. van der Heijden , Eline Houben , Frederike J. Bemelman , Annette E. Neele , Perry D. Moerland , Liffert Vogt , Jeffrey Kroon , Marc L. Hilhorst
{"title":"ANCA相关性血管炎的心血管风险：单核细胞表型揭示血清学亚群之间的独特特征","authors":"Yosta Vegting , Katie ML. Hanford , Aldo Jongejan , Gayle RS. Gajadin , Miranda Versloot , Nelly D. van der Bom-Baylon , Tamara Dekker , E. Lars Penne , Joost W. van der Heijden , Eline Houben , Frederike J. Bemelman , Annette E. Neele , Perry D. Moerland , Liffert Vogt , Jeffrey Kroon , Marc L. Hilhorst","doi":"10.1016/j.atherosclerosis.2024.118559","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aims</h3><p>Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV.</p></div><div><h3>Methods</h3><p>A cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An <em>in vitro</em> transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes.</p></div><div><h3>Results</h3><p>Monocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. During active disease, PR3-AAV was linked with elevated serum CRP and increased platelet counts compared to MPO-AAV.</p></div><div><h3>Conclusions</h3><p>These findings highlight changes in monocyte subset composition and activation, but not in the intrinsic migration capacity of AAV monocytes. MPO-AAV monocytes are associated with sustained upregulation of inflammatory genes, whereas PR3-AAV monocytes exhibit chemokine receptor upregulation. These molecular changes may play a role in elevating cardiovascular risk as well as in the underlying pathophysiology of AAV.</p></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"397 ","pages":"Article 118559"},"PeriodicalIF":4.9000,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0021915024011316/pdfft?md5=3eb0d1af171ef2c99038d78b4b69c529&pid=1-s2.0-S0021915024011316-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Cardiovascular risk in ANCA-associated vasculitis: Monocyte phenotyping reveals distinctive signatures between serological subsets\",\"authors\":\"Yosta Vegting , Katie ML. Hanford , Aldo Jongejan , Gayle RS. Gajadin , Miranda Versloot , Nelly D. van der Bom-Baylon , Tamara Dekker , E. Lars Penne , Joost W. van der Heijden , Eline Houben , Frederike J. Bemelman , Annette E. Neele , Perry D. Moerland , Liffert Vogt , Jeffrey Kroon , Marc L. Hilhorst\",\"doi\":\"10.1016/j.atherosclerosis.2024.118559\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and aims</h3><p>Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV.</p></div><div><h3>Methods</h3><p>A cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An <em>in vitro</em> transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes.</p></div><div><h3>Results</h3><p>Monocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. 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Cardiovascular risk in ANCA-associated vasculitis: Monocyte phenotyping reveals distinctive signatures between serological subsets
Background and aims
Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV.
Methods
A cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An in vitro transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes.
Results
Monocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. During active disease, PR3-AAV was linked with elevated serum CRP and increased platelet counts compared to MPO-AAV.
Conclusions
These findings highlight changes in monocyte subset composition and activation, but not in the intrinsic migration capacity of AAV monocytes. MPO-AAV monocytes are associated with sustained upregulation of inflammatory genes, whereas PR3-AAV monocytes exhibit chemokine receptor upregulation. These molecular changes may play a role in elevating cardiovascular risk as well as in the underlying pathophysiology of AAV.
期刊介绍：
Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review.
Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.
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