Abstract
Aortic valve stenosis (AS) is characterized by extensive calcification of the aortic valve leaflets and infiltration of inflammatory cells. Activated mast cells (MCs) may participate in the induction of fibrosis and calcification with ensuing valve stiffening. We sought to investigate whether the number of MCs within stenotic aortic valves is associated with the severity of AS. We studied 43 patients (19 men, 24 women) with dominant AS (age, 64.2 ± 5.9 years; mean transvalvular pressure gradient, 62.11 ± 24.47 mmHg) without atherosclerotic vascular disease, undergoing elective aortic valve replacement. MCs were detected in the excised valves by immunostaining. Aortic valves from five healthy subjects obtained on autopsy served as negative controls. The number of tryptase- and chymase-positive MCs was increased in AS valves compared with the control valves (6.9 [2.3–18.9]/mm2 vs. 0.7 [0–2.2]/mm2, P = 0.0001 and 3.2 [2.1–9.4]/mm2 vs. 0.3 [0–1.9]/mm2, P = 0.002, respectively). MCs that colocalized with macrophages and neovessels were detected mainly in the calcified regions of the leaflets. The number of MCs positively correlated with maximal (r = 0.73, P < 0.0001) and mean (r = 0.78, P < 0.0001) gradients and maximal aortic jet velocity (r = 0.68, P = 0.0005). An inverse correlation with aortic valve area (r = −0.71, P = 0.0001) was also observed. Multivariate regression analysis revealed that MC number and valve thickness were significantly associated with mean transvalvular gradient (R 2 = 0.74, P < 0.000001) in AS patients. Increased MC number within human stenotic aortic valves is associated with the severity of AS.
Highlights
Aortic valve stenosis (AS) is a common cardiac valve acquired defect in older subjects
We demonstrate that increased mast cells (MCs) numbers within human stenotic aortic valves, mainly in calcified areas, are associated with the severity of AS
This study is the first to show that the higher the number of MCs, the more severe AS is in subjects without evidence of atherosclerotic vascular disease
Summary
Aortic valve stenosis (AS) is a common cardiac valve acquired defect in older subjects. The narrowing of the valve opening that occurs as a result of calcification is related to the high pressure gradient across the stenotic valve [1]. In recent years AS has been perceived as an active inflammatory process that shares many similarities with atherosclerosis, including subendothelial accumulation of oxidized lipoproteins, calcification [2], and infiltration of inflammatory cells, in particular T cells, macrophages [3], and mast cells (MCs) [4]. MCs are able to synthesize a large number of proinflammatory and profibrotic mediators, followed. MC-derived chymase can stimulate angiotensin II formation [4]. Increased Ang II production, in turn, may mediate collagen gene transcription by stimulating the expression of transforming growth factor-β (TGF-β) [4]. TGF-β1 was shown to be characteristically accumulated in MCs [4] as well as in the extracellular matrix and mineral deposits in calcified
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