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Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients
- Source :
- Cells, Volume 9, Issue 1, Dipòsit Digital de la UB, Universidad de Barcelona, Cells, Vol 9, Iss 1, p 154 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI, 2020.
-
Abstract
- Background: Marfan syndrome (MFS) is a genetic disease, characterized by thoracic aortic aneurysm (TAA), which treatment is to date purely surgical. Understanding of novel molecular targets is mandatory to unveil effective pharmacological approaches. Cyclophilin A (CyPA) and its receptor EMMPRIN are associated with several cardiovascular diseases, including abdominal aortic aneurysm. Here, we envisioned the contribution of CyPA/EMMPRIN axis in MFS-related TAA. Methods: We obtained thoracic aortic samples from healthy controls (HC) and MFS patients&rsquo<br />aortas and then isolated vascular smooth muscle cells (VSMC) from the aortic wall. Results: our findings revealed that MFS aortic tissue samples isolated from the dilated zone of aorta showed higher expression levels of EMMPRIN vs. MFS non-dilated aorta and HC. Interestingly, angiotensin II significantly stimulated CyPA secretion in MFS-derived VSMC (MFS-VSMC). CyPA treatment on MFS-VSMC led to increased levels of EMMPRIN and other MFS-associated pro-fibrotic mediators, such as TGF-&beta<br />1 and collagen I. These molecules were downregulated by in vitro treatment with CyPA inhibitor MM284. Our results suggest that CyPA/EMMPRIN axis is involved in MFS-related TAA development, since EMMPRIN is upregulated in the dilated zone of MFS patients&rsquo<br />TAA and the inhibition of its ligand, CyPA, downregulated EMMPRIN and MFS-related markers in MFS-VSMC. Conclusions: these insights suggest both a novel detrimental role for CyPA/EMMPRIN axis and its inhibition as a potential therapeutic strategy for MFS-related TAA treatment.
- Subjects :
- 0301 basic medicine
Marfan syndrome
musculoskeletal diseases
congenital, hereditary, and neonatal diseases and abnormalities
EMMPRIN
Aortic aneurysms
thoracic aortic aneurysm
Cypa
macromolecular substances
030204 cardiovascular system & hematology
Thoracic aortic aneurysm
Article
Marfan Syndrome
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
Fibrosis
medicine.artery
Genetics
Humans
Medicine
vascular smooth muscle cells
cardiovascular diseases
Receptor
skin and connective tissue diseases
lcsh:QH301-705.5
Aorta
Aortic Aneurysm, Thoracic
biology
business.industry
fibrosis
General Medicine
medicine.disease
biology.organism_classification
Angiotensin II
Abdominal aortic aneurysm
030104 developmental biology
lcsh:Biology (General)
Case-Control Studies
Basigin
Cancer research
cardiovascular system
Aneurismes aòrtics
business
Cyclophilin A
Genètica
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cells, Volume 9, Issue 1, Dipòsit Digital de la UB, Universidad de Barcelona, Cells, Vol 9, Iss 1, p 154 (2020)
- Accession number :
- edsair.doi.dedup.....9253c65cbbf994d183ab659eee68e1e8