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.

MAZZONE A., M., EPISTOLATO M., C., DE CATERINA, R., Storti, S., Vittorini, S., Sbrana, S., et al. (2004). Neoangiogenesis, T-lymphocyte infiltration, and Heat Shock Protein-60 are biologicla hallmarks of an immunomediated inflammaory process in end-stage calcified aortic valve stenosis. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 43, 1670-1676 [10.1016/j.jacc.2003.12.041].

Neoangiogenesis, T-lymphocyte infiltration, and Heat Shock Protein-60 are biologicla hallmarks of an immunomediated inflammaory process in end-stage calcified aortic valve stenosis

TANGANELLI, PIERO
2004

Abstract

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.
MAZZONE A., M., EPISTOLATO M., C., DE CATERINA, R., Storti, S., Vittorini, S., Sbrana, S., et al. (2004). Neoangiogenesis, T-lymphocyte infiltration, and Heat Shock Protein-60 are biologicla hallmarks of an immunomediated inflammaory process in end-stage calcified aortic valve stenosis. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 43, 1670-1676 [10.1016/j.jacc.2003.12.041].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/26242
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