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). Ten human BAVc and nine TAVc were collected from male who underwent primary aortic valve replacement. Eight TAVn were obtained from male who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were up-regulated and none were down-regulated in BAVc compared to TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid valves. There were 462 genes up-regulated and 282 down-regulated in BAVc compared to TAVn. In TAVc compared to TAVn, 329 genes were up- and 170 were down-regulated. A total of 273 up-regulated and 147 down-regulated 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 to 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.
- Calcific aortic valve disease
- calcific aortic valve stenosis
- RNA sequencing
- bicuspid aortic valve
- Copyright © 2016, Physiological Genomics