CLINICAL RESEARCH: VALVULAR HEART DISEASE
Neoangiogenesis, T-lymphocyte infiltration, and heat shock protein-60 are biological hallmarks of an immunomediated inflammatory process in end-stage calcified aortic valve stenosis
Annamaria Mazzone, MD*,*,
Maria Carmela Epistolato, BSc ,
Raffaele De Caterina, MD, PhD,
Simona Storti, BSc ,
Simona Vittorini, PhD*,
Silverio Sbrana, MD, PhD*,
Jacopo Gianetti, MD, PhD*,
Stefano Bevilacqua, MD*,
Mattia Glauber, MD*,
Andrea Biagini, MD* and
Piero Tanganelli, MD
* CNR Institute of Clinical Physiology, Ospedale Pasquinucci, Massa, Italy
Department of Pathology, University of Siena, Siena, Italy
Chair of Cardiology, "G. d'Annunzio" University, Chieti, Italy
Manuscript received May 30, 2003;
revised manuscript received November 26, 2003,
accepted December 1, 2003.
* Reprint requests and correspondence: Dr. Annamaria Mazzone, Department of Cardiology and Cardiac Surgery, Ospedale G. Pasquinucci, 54100 Massa, Italy.
mazzone{at}ifc.cnr.it
OBJECTIVES: We investigated the main biomolecular features in the evolution of aortic stenosis, focusing on advanced lesions.
BACKGROUND: "Degenerative" aortic valve stenosis shares risk factors and inflammatory similarities with atherosclerosis.
METHODS: We compared nonrheumatic stenotic aortic valves from 26 patients undergoing surgical valve replacement (group A) and 14 surgical control patients (group B). We performed semiquantitative histological and immunohistochemical analyses on valve leaflets to measure inflammation, sclerosis, calcium, neoangiogenesis, and intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. We assessed heat shock protein 60 (hsp60) gene expression as an index of cellular stress and C-reactive protein, erythrocyte sedimentation rate, and fibrinogen as systemic inflammatory markers.
RESULTS: In group A valves, we found a prevalence of calcium nodules surrounded by activated inflammatory infiltrates, neovessels, and abundant ICAM-1, VCAM-1, and hsp60 gene expression. Specimens from group B were negative for all of these markers, except 2 of 14 positivity for hsp60. The presence of active inflammatory infiltrates correlated with an abundance of thin neovessels (p < 0.01) and hsp60 gene expression (p = 0.01), whereas neoangiogenesis correlated with inflammation (p = 0.04), calcium (p = 0.01), and hsp60 gene expression (p = 0.04).
CONCLUSIONS: "Degenerative" aortic valve stenosis appears to be a chronic inflammatory process associated with atherosclerotic risk factors. The coexistence of neoangiogenesis, T-lymphocyte infiltration, adhesion molecules, and hsp60 gene expression indicates an active immunomediated process in the final phases of the disease.
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Abbreviations and Acronyms
| | CRP | = C-reactive protein | | DNA | = deoxyribonucleic acid | | ESR | = erythrocyte sedimentation rate | | GAPDH | = glyceraldehyde-3-phosphate dehydrogenase | | HE | = hematoxylin-eosin | | hsp60 | = heat shock protein-60 | | ICAM-1 | = intercellular adhesion molecule-1 | | LDL | = low-density lipoprotein | | mRNA | = messenger ribonucleic acid | | PBS | = phosphate-buffered saline | | PCR | = polymerase chain reaction | | RT | = reverse transcription | | VCAM-1 | = vascular cell adhesion molecule-1 | | WVG | = Weigert-van Gieson |
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