TY - JOUR
T1 - Understanding the structural features of symptomatic calcific aortic valve stenosis
T2 - A broad-spectrum clinico-pathologic study in 236 consecutive surgical cases
AU - Galli, Daniela
AU - Manuguerra, Roberta
AU - Monaco, Rodolfo
AU - Manotti, Laura
AU - Goldoni, Matteo
AU - Becchi, Gabriella
AU - Carubbi, Cecilia
AU - Vignali, Giulia
AU - Cucurachi, Nicola
AU - Gherli, Tiziano
AU - Nicolini, Francesco
AU - Lorusso, Roberto
AU - Vitale, Marco
AU - Corradi, Domenico
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Background: With age, aortic valve cusps undergo varying degrees of sclerosis which, sometimes, can progress to calcific aortic valve stenosis (AVS). To perform a retrospective clinico-pathologic investigation in patients with calcific AVS.Methods: We characterized and graded the structural remodeling in 236 aortic valves (200 tricuspid and 36 bicuspid) from patients with calcific AVS (148 males; average 72 years); possible relationships between general/clinical/echocardiographic characteristics and the histopathologic changes were explored. Twenty autopsy aortic valves served as controls. In 40 cases, we also tested the immunohistochemical expression of metalloproteinases and cytokines, and characterized the inflammatory infiltrate. In 5 cases, we cultured cusp stem cells and explored their potential to differentiate into osteoblasts/adipocytes.Results: AVS cusps showed structural remodeling as severe fibrosis (100%), calcific nodules (100%), neoangiogenesis (81%), inflammation (71%), bone metaplasia with or without hematopoiesis (6% and 53%, respectively), adipose metaplasia (16%), and cartilaginous metaplasia (7%). At multivariate analysis, AVS degree and interventricular septum thickness were the only predictors of remodeling (barring inflammation). All the tested metalloproteinases (except MMP-13) and cytokines were expressed in AVS cusps. Inflammation mainly consisted of B and T lymphocytes (CD4+/CD8+ cell ratio 3:1) and plasma cells. AVS changes were mostly different from typical atherosclerosis. Cultured mesenchymal cusp stem cells could differentiate into osteoblasts/adipocytes.Conclusions: Structural remodeling in AVS is peculiar and considerable, and is related to the severity of the disease. However, the different newly formed tissues-where "valvular interstitial cells" play a key role-and their wellknown slow turnover suggest a reverse structural remodeling improbable. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
AB - Background: With age, aortic valve cusps undergo varying degrees of sclerosis which, sometimes, can progress to calcific aortic valve stenosis (AVS). To perform a retrospective clinico-pathologic investigation in patients with calcific AVS.Methods: We characterized and graded the structural remodeling in 236 aortic valves (200 tricuspid and 36 bicuspid) from patients with calcific AVS (148 males; average 72 years); possible relationships between general/clinical/echocardiographic characteristics and the histopathologic changes were explored. Twenty autopsy aortic valves served as controls. In 40 cases, we also tested the immunohistochemical expression of metalloproteinases and cytokines, and characterized the inflammatory infiltrate. In 5 cases, we cultured cusp stem cells and explored their potential to differentiate into osteoblasts/adipocytes.Results: AVS cusps showed structural remodeling as severe fibrosis (100%), calcific nodules (100%), neoangiogenesis (81%), inflammation (71%), bone metaplasia with or without hematopoiesis (6% and 53%, respectively), adipose metaplasia (16%), and cartilaginous metaplasia (7%). At multivariate analysis, AVS degree and interventricular septum thickness were the only predictors of remodeling (barring inflammation). All the tested metalloproteinases (except MMP-13) and cytokines were expressed in AVS cusps. Inflammation mainly consisted of B and T lymphocytes (CD4+/CD8+ cell ratio 3:1) and plasma cells. AVS changes were mostly different from typical atherosclerosis. Cultured mesenchymal cusp stem cells could differentiate into osteoblasts/adipocytes.Conclusions: Structural remodeling in AVS is peculiar and considerable, and is related to the severity of the disease. However, the different newly formed tissues-where "valvular interstitial cells" play a key role-and their wellknown slow turnover suggest a reverse structural remodeling improbable. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
KW - Aortic valve stenosis
KW - Structural remodeling
KW - Histopathology
KW - Valvular interstitial cells
KW - Osseous metaplasia
KW - AMERICAN-HEART-ASSOCIATION
KW - ATHEROSCLEROTIC LESIONS
KW - VASCULAR-LESIONS
KW - CARDIAC VALVES
KW - BONE-FORMATION
KW - RISK-FACTORS
KW - ARTERIOSCLEROSIS
KW - CLASSIFICATION
KW - INFLAMMATION
KW - PROGRESSION
U2 - 10.1016/j.ijcard.2016.11.180
DO - 10.1016/j.ijcard.2016.11.180
M3 - Article
C2 - 27866029
SN - 0167-5273
VL - 228
SP - 364
EP - 374
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -