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SPP1/osteopontin :
SPP1/osteopontin : a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?
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- Freiholtz, David (author)
- Karolinska Institutet
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- Bergman, Otto (author)
- Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden
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- Pradhananga, Sailendra (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
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- Lång, Karin (author)
- Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden
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- Poujade, Flore Anne (author)
- Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden
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- Granath, Carl (author)
- Section of Cardiothoracic Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden
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- Olsson, Christian (author)
- Karolinska Institutet
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- Franco-Cereceda, Anders (author)
- Karolinska Institutet
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- Sahlén, Pelin (author)
- KTH,Science for Life Laboratory, SciLifeLab,Genteknologi
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- Eriksson, Per (author)
- Karolinska Institutet
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- Björck, Hanna M. (author)
- Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden
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(creator_code:org_t)
- Springer Nature, 2023
- 2023
- English.
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In: Journal of Molecular Medicine. - : Springer Nature. - 0946-2716 .- 1432-1440. ; 101:10, s. 1323-1333
- Related links:
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https://doi.org/10.1...
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Abstract
Subject headings
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- Abstract: Degenerative ascending aortic aneurysm (AscAA) is a silent and potentially fatal disease characterized by excessive vascular inflammation and fibrosis. We aimed to characterize the cellular and molecular signature for the fibrotic type of endothelial mesenchymal transition (EndMT) that has previously been described in degenerative AscAA. Patients undergoing elective open-heart surgery for AscAA and/or aortic valve repair were recruited. Gene expression in the intima-media of the ascending aorta was measured in 22 patients with non-dilated and 24 with dilated aortas, and candidate genes were identified. Protein expression was assessed using immunohistochemistry. Interacting distal gene enhancer regions were identified using targeted chromosome conformation capture (HiCap) in untreated and LPS-treated THP1 cells, and the associated transcription factors were analyzed. Differential expression analysis identified SPP1 (osteopontin) as a key gene in the signature of fibrotic EndMT in patients with degenerative AscAA. The aortic intima-media expression of SPP1 correlated with the expression of inflammatory markers, the level of macrophage infiltration, and the aortic diameter. HiCap analysis, followed by transcription factor binding analysis, identified ETS1 as a potential regulator of SPP1 expression under inflammatory conditions. In conclusion, the present findings suggest that SPP1 may be involved in the development of the degenerative type of AscAA. Key messages: In the original manuscript titled “SPP1/osteopontin, a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?” by David Freiholtz, Otto Bergman, Saliendra Pradhananga, Karin Lång, Flore-Anne Poujade, Carl Granath, Christian Olsson, Anders Franco-Cereceda, Pelin Sahlén, Per Eriksson, and Hanna M Björck, we present novel findings on regulatory factors on osteopontin (SPP1) expression in immune cells involved in degenerative ascending aortic aneurysms (AscAA). The central findings convey: SPP1 is a potential driver of the fibrotic endothelial-to-mesenchymal transition in AscAA.SPP1/osteopontin expression in AscAA is predominately by immune cells.ETS1 is a regulatory transcription factor of SPP1 expression in AscAA immune cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Aneurysm
- Ascending aorta
- Fibrosis
- Inflammation
- Osteopontin
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Freiholtz, David
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Bergman, Otto
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Pradhananga, Sai ...
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Lång, Karin
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Poujade, Flore A ...
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Granath, Carl
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Olsson, Christia ...
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Franco-Cereceda, ...
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Sahlén, Pelin
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Eriksson, Per
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Björck, Hanna M.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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Journal of Molec ...
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Royal Institute of Technology
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Karolinska Institutet