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 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.
Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients / G.L. Perrucci, E. Rurali, M. Corlianò, M. Balzo, M. Piccoli, D. Moschetta, A. Pini, R. Gaetano, C. Antona, G. Egea, G. Fischer, M. Malešević, F. Alamanni, E. Cogliati, A. Paolin, G. Pompilio, P. Nigro. - In: CELLS. - ISSN 2073-4409. - 9:1(2020), pp. 154.1-154.18.
|Titolo:||Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients|
PERRUCCI, GIANLUCA LORENZO (Corresponding)
|Parole Chiave:||Cyclophilin A; EMMPRIN; fibrosis; thoracic aortic aneurysm; vascular smooth muscle cells|
|Settore Scientifico Disciplinare:||Settore MED/23 - Chirurgia Cardiaca|
|Data di pubblicazione:||2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/cells9010154|
|Appare nelle tipologie:||01 - Articolo su periodico|