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European Heart Journal Advance Access originally published online on January 12, 2008
European Heart Journal 2008 29(3):371-376; doi:10.1093/eurheartj/ehm592
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Association between self-replicating calcifying nanoparticles and aortic stenosis: a possible link to valve calcification

Miguel A. Bratos-Pérez1, Pedro L. Sánchez2,*, Susana García de Cruz1, Eduardo Villacorta3, Igor F. Palacios4, José M. Fernández-Fernández1, Salvatore Di Stefano3, Antonio Orduña-Domingo1, Yolanda Carrascal3, Pedro Mota3, Cándido Martín-Luengo5, Javier Bermejo2, José A. San Roman3, Antonio Rodríguez-Torres1, Francisco Fernández-Avilés on behalf of Grupo AORTICA (Grupo de Estudio de la Estenosis Aórtica)2

1 Servicio de Microbiología, Facultad de Medicina, Hospital Clínico Universitario, Valladolid, Spain
2 Servicio de Cardiología, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007, Madrid, Spain
3 Instituto de Ciencias del Corazón (ICICOR), Hospital Clínico Universitario, Valladolid, Spain
4 Cardiac Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
5 Servicio de Cardiología, Hospital Universitario de Salamanca, Spain

Received 17 July 2007; revised 2 November 2007; accepted 29 November 2007; online publish-ahead-of-print 12 January 2008.

* Corresponding author. Tel: +34 637971999, Fax: +34 915868276, Email: pedrolsanchez{at}secardiologia.es

Aims: Among various hypotheses proposed for pathological tissue calcification, recent evidence supports the possibility that self-replicating calcifying nanoparticles (CNPs) can contribute to such calcification. These CNPs have been detected and isolated from calcified human tissues, including blood vessels and kidney stones, and are referred to as nanobacteria. We evaluated calcific aortic valves for the presence of CNP.

Methods and results: Calcific aortic valves were obtained from 75 patients undergoing surgical valve replacement. The control group was formed by eight aortic valves corresponding to patients with heart transplants. In the microbiology laboratory, valves were screened for CNP using a 4–6 weeks specific culture method. The culture for CNP was positive in 48 of the 75 valves with aortic stenosis (64.0%) in comparison with zero of eight (0%) for the control group (P = 0.0005). The observation of cultures by way of scanning electron microscopy highlighted the resemblance in size and morphology of CNP.

Conclusion: Self-replicating calcific nanometer-scale particles, similar to those described as CNP from other calcific human tissues, can be cultured and visualized from calcific human aortic valves. This finding raises the question as to whether CNP contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

Key Words: Nanobacteria • Calcifying nanoparticles • Aortic stenosis • Calcification


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