Isolated Valve Amyloid Deposition in Aortic Stenosis: Potential Clinical and Pathophysiological Relevance

Author:

Conte Maddalena12ORCID,Poggio Paolo3,Monti Maria45ORCID,Petraglia Laura1,Cabaro Serena1,Bruzzese Dario6ORCID,Comentale Giuseppe7ORCID,Caruso Aurelio2,Grimaldi Mariagabriella2,Zampella Emilia7ORCID,Gencarelli Annarita7,Cervasio Maria Rosaria7,Cozzolino Flora45ORCID,Monaco Vittoria45ORCID,Myasoedova Veronika3ORCID,Valerio Vincenza3,Ferro Adele8,Insabato Luigi7ORCID,Bellino Michele9,Galasso Gennaro9ORCID,Graziani Francesca10,Pucci Pietro4,Formisano Pietro1ORCID,Pilato Emanuele7ORCID,Cuocolo Alberto7ORCID,Perrone Filardi Pasquale7,Leosco Dario1,Parisi Valentina1

Affiliation:

1. Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, Italy

2. Casa di Cura San Michele, 81024 Caserta, Italy

3. Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy

4. Dipartimento di Scienze Chimiche, University of Naples Federico II, 5, 80131 Naples, Italy

5. CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy

6. Department of Public Health, University of Naples Federico II, 5, 80131 Naples, Italy

7. Department of Advanced Biomedical Science, University of Naples Federico II, 5, 80131 Naples, Italy

8. Institute of Biostructure and Bioimaging, CNR, 80145 Naples, Italy

9. Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081 Salerno, Italy

10. Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy

Abstract

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1β which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.

Funder

Italian Ministry of Health funds

Fondazione Gigi e Pupa Ferrari ONLUS

Publisher

MDPI AG

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