title: RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing.
abstract: The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve are unknown. The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid valves. There were 462 genes upregulated and 282 downregulated in BAVc compared with TAVn. In TAVc compared with TAVn, 329 genes were up- and 170 were downregulated. A total of 273 upregulated and 147 downregulated genes were concordantly altered between BAVc vs. TAVn and TAVc vs. TAVn, which represent 56 and 84% of significant genes in the first and second comparisons, respectively. This indicates that extra genes and pathways were altered in BAVc. Shared pathways between calcified (BAVc and TAVc) and normal (TAVn) aortic valves were also more extensively altered in BAVc. The top pathway enriched for genes differentially expressed in calcified compared with normal valves was fibrosis, which support the remodeling process as a therapeutic target. These findings are relevant to understand the molecular basis of AS in patients with bicuspid and tricuspid valves.
authors: Centre de recherche Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec, Canada.
authors: Sandra
authors: 0000-0003-0336-9682
authors: S
authors: Guauque-Olarte
authors: Centre de Recherche du CHU de Québec, Laval University, Quebec, Canada.
authors: Arnaud
authors: A
authors: Droit
authors: Centre de recherche Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec, Canada.
authors: Joël
authors: J
authors: Tremblay-Marchand
authors: Centre de recherche Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec, Canada.
authors: Nathalie
authors: N
authors: Gaudreault
authors: Centre de recherche Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec, Canada.
authors: Dimitri
authors: D
authors: Kalavrouziotis
authors: Centre de recherche Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec, Canada.
authors: Francois
authors: F
authors: Dagenais
authors: Harvard Medical School, Boston, Massachusetts, and.
authors: Jonathan G
authors: JG
authors: Seidman
authors: Harvard Medical School, Boston, Massachusetts, and.
authors: Simon C
authors: SC
authors: Body
authors: Centre de recherche Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec, Canada.
authors: Philippe
authors: P
authors: Pibarot
authors: Centre de recherche Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec, Canada.
authors: Patrick
authors: P
authors: Mathieu
authors: Centre de recherche Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec, Canada; Department of Molecular Medicine, Laval University, Quebec, Canada yohan.bosse@criucpq.ulaval.ca.
authors: Yohan
authors: Y
authors: Bossé
mesh_terms: D001021:Aortic Valve / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D001024:Aortic Valve Stenosis; D000082882:Bicuspid Aortic Valve Disease; D002114:Calcinosis; D015536:Down-Regulation / Q000235:genetics; D006349:Heart Valve Diseases / Q000378:metabolism*; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D017423:Sequence Analysis, RNA / Q000379:methods; D059467:Transcriptome / Q000235:genetics*; D014261:Tricuspid Valve / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D012333:RNA, Messenger
keywords: RNA sequencing; bicuspid aortic valve; calcific aortic valve disease; calcific aortic valve stenosis; gene expression; pathways; transcriptome