BACKGROUND: The development of @entity472 is not only associated with @entity730 and extracellular matrix remodeling, but also with @entity32 . The aim of this study was to determine the role of proinflammatory signaling through the leukotriene (LT) pathway in @entity472 . METHODS AND RESULTS: After macroscopic dissection of surgically removed @entity1 aortic valves, RNA was extracted from 311 preparations derived from 68 @entity1 to differentiate normal, thickened, and calcified areas from each cusp. Subsequently, quantitative polymerase chain reaction analysis was used to correlate gene expression patterns with preoperative echocardiographic parameters. The messenger RNA levels of the LT-forming enzyme @entity1437 increased 1.6- and 2.2-fold in thickened and calcified tissue, respectively, compared with normal areas of the same valves. In thickened tissues, messenger RNA levels for @entity1437 (r= -0.35; P=0.03), its activating protein @entity1437 activating protein; r= -0.39; P=0.02), and @entity19960 (r= -0.48; P=0.01) correlated inversely with the velocity-time integral ratio. In addition, @entity19960 transcripts correlated inversely with aortic valve area, indexed for body surface area (r= -0.52; P=0.007). Immunohistochemical stainings revealed LT receptor expression on valvular myofibroblasts. In primary cultures of @entity1 myofibroblasts derived from stenotic aortic valves, @entity223 (LTC(4)) increased intracellular @entity460 , enhanced reactive @entity26 species production, reduced the mitochondrial membrane potential, and led to morphological cell cytoplasm changes and @entity730 . CONCLUSIONS: The upregulation of the LT pathway in @entity1 @entity472 and its correlation with clinical @entity850 severity, taken together with the potentially detrimental LT-induced effects on valvular myofibroblasts, suggests one possible role of @entity32 in the development of @entity472 .

Upregulation of the @entity1437 pathway in XXXX aortic valves correlates with severity of @entity850 and leads to leukotriene-induced effects on valvular myofibroblasts.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity1437 :: ('240', 'Gene') :: ['(5-lipoxygenase', '5-lipoxygenase'] @entity850 :: ('MESH:D003251', 'Disease') :: ['stenosis'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity730 :: ('MESH:D002114', 'Disease') :: ['calcification'] @entity223 :: ('MESH:D017997', 'Chemical') :: ['Leukotriene C(4)'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity472 :: ('MESH:D001024', 'Disease') :: ['aortic stenosis', 'aortic valve stenosis'] @entity19960 :: ('4048', 'Gene') :: ['LTA(4) hydrolase', 'leukotriene A(4) hydrolase']
@entity1 :: (9606,Species) :: ['human']
