Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients

Gianluca L Perrucci, Erica Rurali, Maria Corlianò, Maria Balzo, Michela Piccoli, Donato Moschetta, Alessandro Pini, Raffaella Gaetano, Carlo Antona, Gustavo Egea, Gunter Fischer, Miroslav Malešević, Francesco Alamanni, Elisa Cogliati, Adolfo Paolin, Giulio Pompilio, Patrizia Nigro

Research output: Contribution to journalArticlepeer-review


: 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.

Original languageEnglish
Issue number1
Publication statusPublished - Jan 8 2020


  • Aortic Aneurysm, Thoracic/metabolism
  • Basigin/metabolism
  • Case-Control Studies
  • Cyclophilin A/metabolism
  • Fibrosis/metabolism
  • Humans
  • Marfan Syndrome/physiopathology
  • Transforming Growth Factor beta1/metabolism


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