Theranostics 2019; 9(8):2224-2234. doi:10.7150/thno.30714

Research Paper

Soluble EMMPRIN levels discriminate aortic ectasia in Marfan syndrome patients

Erica Rurali1✉, Gianluca L. Perrucci1,2, Raffaella Gaetano3, Alessandro Pini4, Donato Moschetta1, Davide Gentilini5,6, Patrizia Nigro1*, Giulio Pompilio1,2,7*

1. Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino IRCCS, Milan, Italy
2. Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Italy
3. Istituto di Biomedicina ed Immunologia Molecolare "Alberto Monroy", CNR, Palermo, Italy
4. Rare Disease Center, Marfan Clinic, Cardiology department, ASST-FBF-Sacco, Milan, Italy
5. Molecular Biology Laboratory, Unit of Bioinformatic and Statistical Genomic, Istituto Auxologico Italiano IRCCS, Cusano Milanino, Italy
6. Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
7. Department of Cardiovascular Surgery, Centro Cardiologico Monzino IRCCS, Milan, Italy
*Equally contributed as last author

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Rurali E, Perrucci GL, Gaetano R, Pini A, Moschetta D, Gentilini D, Nigro P, Pompilio G. Soluble EMMPRIN levels discriminate aortic ectasia in Marfan syndrome patients. Theranostics 2019; 9(8):2224-2234. doi:10.7150/thno.30714. Available from

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Marfan syndrome (MFS) is a rare genetic disease characterized by a matrix metalloproteases (MMPs) dysregulation that leads to extracellular matrix degradation. Consequently, MFS patients are prone to develop progressive thoracic aortic enlargement and detrimental aneurysm. Since MMPs are activated by the extracellular MMP inducer (EMMPRIN) protein, we determined whether its plasmatic soluble form (sEMMPRIN) may be considered a marker of thoracic aortic ectasia (AE).

Methods: We compared plasma sEMMPRIN levels of 42 adult Caucasian MFS patients not previously subjected to aortic surgery with those of matched healthy controls (HC) by ELISA. In the MFS cohort we prospectively evaluated the relationship between plasma sEMMPRIN levels and the main MFS-related manifestations.

Results: MFS patients had lower plasma sEMMPRIN levels (mean±SD: 2071±637 pg/ml) than HC (2441±642 pg/ml, p=0.009). Amongst all considered MFS-related clinical features, we found that only aortic root dilatation associated with circulating sEMMPRIN levels. Specifically, plasma sEMMPRIN levels negatively correlated with aortic Z-score (r=-0.431, p=0.004), and were significantly lower in patients with AE (Z-score≥2, 1788±510 pg/ml) compared to those without AE (Z-score<2, 2355±634 pg/ml; p=0.003). ROC curve analysis revealed that plasma sEMMPRIN levels discriminated patients with AE (AUC [95%CI]: 0.763 [0.610-0.916], p=0.003) with 85.7% sensitivity, 76.2% specificity, and 81% accuracy. We defined plasma sEMMPRIN levels ≤2246 pg/ml as the best threshold discriminating the presence of AE in MFS patients with an odds ratio [95%CI] of 19.2 [3.947-93.389] (p<0.001).

Conclusions: MFS patients are characterized by lower sEMMPRIN levels than HC. Notably, plasma sEMMPRIN levels are strongly associated with thoracic AE.

Keywords: Marfan syndrome, aortic ectasia, EMMPRIN, thoracic aortic aneurysm, Z-score.