Calcific aortic valve disease (CAVD) is the most frequent heart valve disorder. Studies indicate that mineralization of the aortic valve may be related to the inflammatory process. However, no clear evidence has been given regarding clinical evolution of aortic stenosis and the inflammatory process within the aortic valve. Aortic valves excised from 285 patients with CAVD undergoing aortic valve replacement were analyzed for the presence of chronic inflammatory infiltrates, and those findings were related to the hemodynamic severity of aortic stenosis. In a subset of 57 patients, in whom additional valvular tissue and the clinical progression rate of aortic stenosis were available, the density of leukocytes was determined as well as the number of TNF-α transcripts. Histological analyses revealed that in 81 (28.4 %) patients, the presence of chronic inflammatory infiltrates was documented within CAVD tissue, which was characterized by the existence of a cluster of cells as well as the presence of neovascularisation and osseous metaplasia. The presence of an inflammatory process within the CAVD tissue was independently related to the remodeling process and the peak transaortic gradient. In addition, the density of leukocytes within CAVD tended to correlate (r = 0.25, p = 0.05) with the progression rate of aortic stenosis. Dense inflammatory infiltrate within CAVD is associated with an active remodeling process, the severity of aortic stenosis, and the hemodynamic progression rate.

Background-Calcific aortic valve stenosis (AS) is a major societal and economic burden that is rising after the current shift toward an older population. Understanding the pathobiology of AS is crucial to implementing better preventive and therapeutic options. Research conducted during the past decade clearly points to active molecular and cellular processes involved in disease pathogenesis. However, no genomic approaches were used to identify genes and pathways that are differentially regulated in aortic valves of patients with and without AS. Methods and Results-A large-scale quantitative measurements of gene expression was performed on 5 normal and 5 AS valves using Affymetrix GeneChips. A total of 409 and 306 genes were significantly up-and downregulated in AS valves, respectively. The 2 most highly upregulated genes were matrix metalloproteinase 12 and chitinase 3-like 1. The upregulation of these 2 biologically relevant genes in AS was validated by real-time polymerase chain reaction in 38 aortic valves (12 normal and 26 AS). To provide a global biological validation of the whole-genome gene expression analysis, the microarray experiment was repeated in a second set of aortic valves with (nϭ5) or without (nϭ5) AS. There was an overrepresentation of small P values among genes claimed significant in the first microarray experiment. A total of 223 genes were replicated (PϽ0.05 and fold change Ͼ1.2), including matrix metalloproteinase 12 and chitinase 3-like 1. Conclusions-This study reveals many unrecognized genes potentially implicated in the pathogenesis of AS. These new genes were overlaid on known pathological pathways leading to AS to refine our molecular understanding of this disease. (Circ Cardiovasc Genet. 2009;2:489-498.)Key Words: aortic valve Ⅲ microarray Ⅲ real-time PCR Ⅲ pathways analyses Ⅲ candidate genes C alcific aortic valve disease is a growing health problem with important clinical consequences. 1 The condition is initiated with focal subendothelial lesions on the aortic side of the leaflet, similar to atherosclerosis plaques, which eventually progress to aortic stenosis (AS). Histopathologically, AS is characterized by massive calcification and fibrous thickening of the valve cusps leading to left ventricular outflow tract obstruction. 2,3 Patients with AS have an 80% risk of valve replacement, progression to heart failure, or death in the next 5 years after diagnosis. 4 A rapid increase in the incidence of hospitalization because of AS was noticed during the past decades. 1 In the same timeframe, there was also a marked increase in the number of aortic valve replacement procedures. The cost associated with these surgical procedures is very high. 5 In addition, as the prevalence of the disease increases markedly with age, 6 the population at risk rises in proportion to the improvement in life expectancy. Accordingly, AS is now a major societal and economic burden that is likely to be substantiated in a near future. It is thus an urgent priority to understand the pathobiological processes l...

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Patients with increased WC combined with elevated C-reactive protein levels are at higher risk for POAF. Thus, interventions targeting inflammation related to visceral obesity might help reducing the incidence of POAF.