Transcriptional Profiling of Normal, Stenotic, and Regurgitant Human Aortic Valves
Copyright policy )Transcriptional Profiling of Normal, Stenotic, and Regurgitant Human Aortic Valves
The genetic mechanisms underlying aortic stenosis (AS) and aortic insufficiency (AI) disease progression remain unclear. We hypothesized that normal aortic valves and those with AS or AI all exhibit unique transcriptional profiles. Normal control (NC) aortic valves were collected from non-matched donor hearts that were otherwise acceptable for transplantation (n = 5). Valves with AS or AI (n = 5, each) were collected from patients undergoing surgical aortic valve replacement. High-throughput sequencing of total RNA revealed 6438 differentially expressed genes (DEGs) for AS vs. NC, 4994 DEGs for AI vs. NC, and 2771 DEGs for AS vs. AI. Among 21 DEGs of interest, APCDD1L, CDH6, COL10A1, HBB, IBSP, KRT14, PLEKHS1, PRSS35, and TDO2 were upregulated in both AS and AI compared to NC, whereas ALDH1L1, EPHB1, GPX3, HIF3A, and KCNT1 were downregulated in both AS and AI (p < 0.05). COL11A1, H19, HIF1A, KCNJ6, PRND, and SPP1 were upregulated only in AS, and NPY was downregulated only in AS (p < 0.05). The functional network for AS clustered around ion regulation, immune regulation, and lipid homeostasis, and that for AI clustered around ERK1/2 regulation. Overall, we report transcriptional profiling data for normal human aortic valves from non-matched donor hearts that were acceptable for transplantation and demonstrated that valves with AS and AI possess unique genetic signatures. These data create a roadmap for the development of novel therapeutics to treat AS and AI.
Adult, Male, Transcription, Genetic, Constriction, Pathologic, Article, Humans, Gene Regulatory Networks, RNA-Seq, transcriptional profiling, Aged, aortic stenosis, Calcinosis, High-Throughput Nucleotide Sequencing, RNA sequencing, Aortic Valve Stenosis, Middle Aged, aortic insufficiency, Aortic Valve Disease, Gene Expression Regulation, Aortic Valve, Heart Transplantation, Female
Adult, Male, Transcription, Genetic, Constriction, Pathologic, Article, Humans, Gene Regulatory Networks, RNA-Seq, transcriptional profiling, Aged, aortic stenosis, Calcinosis, High-Throughput Nucleotide Sequencing, RNA sequencing, Aortic Valve Stenosis, Middle Aged, aortic insufficiency, Aortic Valve Disease, Gene Expression Regulation, Aortic Valve, Heart Transplantation, Female
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).23 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!