We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients.
- Authors
Perrucci, Gianluca L.; Rurali, Erica; Corlianò, Maria; Balzo, Maria; Piccoli, Michela; Moschetta, Donato; Pini, Alessandro; Gaetano, Raffaella; Antona, Carlo; Egea, Gustavo; Fischer, Gunter; Malešević, Miroslav; Alamanni, Francesco; Cogliati, Elisa; Paolin, Adolfo; Pompilio, Giulio; Nigro, Patrizia
- 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’ 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-β1 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’ TAA and 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
THORACIC aneurysms; MARFAN syndrome; CYCLOPHILINS; VASCULAR smooth muscle; GENETIC disorders
- Publication
Cells (2073-4409), 2020, Vol 9, Issue 1, p1
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells9010154