Molecular insights into the relationship between sustained CRP elevation and endothelial dysfunction in axial spondyloarthritis
Objectives To investigate the impact of sustained C reactive protein (CRP) elevation on cardiovascular (CV) risk factors, particularly endothelial dysfunction and atherosclerosis, in axial spondyloarthritis (axSpA) patients and to explore the underlying molecular mechanisms.Methods 245 axSpA patient...
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BMJ Publishing Group
2025-07-01
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| author | Clementina López-Medina Nuria Barbarroja Alejandro Escudero-Contreras Chary López-Pedrera Carlos Perez-Sanchez Pedro Segui Eduardo Collantes Jerusalem Calvo Lourdes Ladehesa-Pineda Desiree Ruíz-Vilchez Laura Cuesta-López Iván Arias-de la Rosa Jesús Eduardo Martín-Salazar Antonio Manuel Barranco Miriam Ruiz-Ponce María Ángeles Puche Larrubia Rafaela Ortega María Carmen Ábalos-Aguilera Elena Moreno-Caño Pedro Ortiz-Buitrago |
| author_facet | Clementina López-Medina Nuria Barbarroja Alejandro Escudero-Contreras Chary López-Pedrera Carlos Perez-Sanchez Pedro Segui Eduardo Collantes Jerusalem Calvo Lourdes Ladehesa-Pineda Desiree Ruíz-Vilchez Laura Cuesta-López Iván Arias-de la Rosa Jesús Eduardo Martín-Salazar Antonio Manuel Barranco Miriam Ruiz-Ponce María Ángeles Puche Larrubia Rafaela Ortega María Carmen Ábalos-Aguilera Elena Moreno-Caño Pedro Ortiz-Buitrago |
| author_sort | Clementina López-Medina |
| collection | DOAJ |
| description | Objectives To investigate the impact of sustained C reactive protein (CRP) elevation on cardiovascular (CV) risk factors, particularly endothelial dysfunction and atherosclerosis, in axial spondyloarthritis (axSpA) patients and to explore the underlying molecular mechanisms.Methods 245 axSpA patients were enrolled. Carotid intima-media thickness (CIMT) and microvascular endothelial function (post-ischaemic reactive hyperaemia) were measured. Retrospective CRP measurements from the past 5 years classified patients as having sustained high CRP if >50% of readings were elevated. Serum levels of 184 inflammation and CV disease-related proteins were analysed using a proximity extension assay, and in vitro studies were conducted in human umbilical vein endothelial cells.Results 40% of axSpA patients had sustained CRP elevation, showing increased metabolic comorbidities, higher prevalence of atherosclerotic plaques and worse microvascular endothelial function compared with those with intermittent CRP elevations. Proteomic analysis identified 10 altered proteins, with interleukin 6 (IL-6) and CUB domain-containing protein 1 (CDCP-1) linked to endothelial dysfunction, higher CIMT and metabolic disturbances. Paraoxonase 3 (PON-3), the only downregulated protein, showed anti-inflammatory, antioxidant and antiatherogenic properties, restoring endothelial function in vitro. CDCP-1 was associated with atherosclerotic plaques and promoted endothelial adhesion, oxidative stress and inflammation in vitro. Anti-TNF-α therapy reduced inflammatory markers, complement components and the atherogenic index, while increasing high density lipoprotein, apolipoprotein A and PON-3 levels and decreasing IL-6 and CDCP-1 levels.Conclusions Sustained CRP elevation in axSpA is strongly linked to increased CV risk, endothelial dysfunction and atherosclerosis. IL-6, CDCP-1 and PON-3 emerge as key mediators connecting inflammation to CV risk. Anti-tumour necrosis factor-α therapy improved the metabolic and inflammatory profile and modulated IL-6, CDCP-1 and PON-3 levels, supporting its role in managing CV risks in axSpA. |
| format | Article |
| id | doaj-art-80ff2d682c874ad2994394d7d833a7c5 |
| institution | Kabale University |
| issn | 2056-5933 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
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| series | RMD Open |
| spelling | doaj-art-80ff2d682c874ad2994394d7d833a7c52025-08-20T03:30:13ZengBMJ Publishing GroupRMD Open2056-59332025-07-0111310.1136/rmdopen-2025-005746Molecular insights into the relationship between sustained CRP elevation and endothelial dysfunction in axial spondyloarthritisClementina López-Medina0Nuria Barbarroja1Alejandro Escudero-Contreras2Chary López-Pedrera3Carlos Perez-Sanchez4Pedro Segui5Eduardo Collantes6Jerusalem Calvo7Lourdes Ladehesa-Pineda8Desiree Ruíz-Vilchez9Laura Cuesta-López10Iván Arias-de la Rosa11Jesús Eduardo Martín-Salazar12Antonio Manuel Barranco13Miriam Ruiz-Ponce14María Ángeles Puche Larrubia15Rafaela Ortega16María Carmen Ábalos-Aguilera17Elena Moreno-Caño18Pedro Ortiz-Buitrago19University of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia Hospital, Cordoba, SpainUniversity of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia Hospital, Cordoba, SpainUniversity of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia Hospital, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia Hospital, Cordoba, SpainUniversity of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia Hospital, Cordoba, SpainRadiology, Reina Sofia Hospital, Cordoba, SpainUniversity of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia Hospital, Cordoba, SpainReina Sofia Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Cordoba, SpainReina Sofia Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Cordoba, SpainReina Sofia Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Cordoba, SpainUniversity of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia Hospital, Cordoba, SpainGastroenterology, General Hospital of Tomelloso, Tomelloso, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia Hospital, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia Hospital, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia Hospital, Cordoba, SpainUniversity of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia Hospital, Cordoba, SpainReina Sofia Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Cordoba, SpainReina Sofia Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia Hospital, Cordoba, SpainMaimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia Hospital, Cordoba, SpainObjectives To investigate the impact of sustained C reactive protein (CRP) elevation on cardiovascular (CV) risk factors, particularly endothelial dysfunction and atherosclerosis, in axial spondyloarthritis (axSpA) patients and to explore the underlying molecular mechanisms.Methods 245 axSpA patients were enrolled. Carotid intima-media thickness (CIMT) and microvascular endothelial function (post-ischaemic reactive hyperaemia) were measured. Retrospective CRP measurements from the past 5 years classified patients as having sustained high CRP if >50% of readings were elevated. Serum levels of 184 inflammation and CV disease-related proteins were analysed using a proximity extension assay, and in vitro studies were conducted in human umbilical vein endothelial cells.Results 40% of axSpA patients had sustained CRP elevation, showing increased metabolic comorbidities, higher prevalence of atherosclerotic plaques and worse microvascular endothelial function compared with those with intermittent CRP elevations. Proteomic analysis identified 10 altered proteins, with interleukin 6 (IL-6) and CUB domain-containing protein 1 (CDCP-1) linked to endothelial dysfunction, higher CIMT and metabolic disturbances. Paraoxonase 3 (PON-3), the only downregulated protein, showed anti-inflammatory, antioxidant and antiatherogenic properties, restoring endothelial function in vitro. CDCP-1 was associated with atherosclerotic plaques and promoted endothelial adhesion, oxidative stress and inflammation in vitro. Anti-TNF-α therapy reduced inflammatory markers, complement components and the atherogenic index, while increasing high density lipoprotein, apolipoprotein A and PON-3 levels and decreasing IL-6 and CDCP-1 levels.Conclusions Sustained CRP elevation in axSpA is strongly linked to increased CV risk, endothelial dysfunction and atherosclerosis. IL-6, CDCP-1 and PON-3 emerge as key mediators connecting inflammation to CV risk. Anti-tumour necrosis factor-α therapy improved the metabolic and inflammatory profile and modulated IL-6, CDCP-1 and PON-3 levels, supporting its role in managing CV risks in axSpA.https://rmdopen.bmj.com/content/11/3/e005746.full |
| spellingShingle | Clementina López-Medina Nuria Barbarroja Alejandro Escudero-Contreras Chary López-Pedrera Carlos Perez-Sanchez Pedro Segui Eduardo Collantes Jerusalem Calvo Lourdes Ladehesa-Pineda Desiree Ruíz-Vilchez Laura Cuesta-López Iván Arias-de la Rosa Jesús Eduardo Martín-Salazar Antonio Manuel Barranco Miriam Ruiz-Ponce María Ángeles Puche Larrubia Rafaela Ortega María Carmen Ábalos-Aguilera Elena Moreno-Caño Pedro Ortiz-Buitrago Molecular insights into the relationship between sustained CRP elevation and endothelial dysfunction in axial spondyloarthritis RMD Open |
| title | Molecular insights into the relationship between sustained CRP elevation and endothelial dysfunction in axial spondyloarthritis |
| title_full | Molecular insights into the relationship between sustained CRP elevation and endothelial dysfunction in axial spondyloarthritis |
| title_fullStr | Molecular insights into the relationship between sustained CRP elevation and endothelial dysfunction in axial spondyloarthritis |
| title_full_unstemmed | Molecular insights into the relationship between sustained CRP elevation and endothelial dysfunction in axial spondyloarthritis |
| title_short | Molecular insights into the relationship between sustained CRP elevation and endothelial dysfunction in axial spondyloarthritis |
| title_sort | molecular insights into the relationship between sustained crp elevation and endothelial dysfunction in axial spondyloarthritis |
| url | https://rmdopen.bmj.com/content/11/3/e005746.full |
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