ABSTRACT
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.
Subject(s)
Aortic Valve Stenosis/genetics , Aortic Valve/metabolism , Gene Regulatory Networks/genetics , Transcription, Genetic , Adult , Aged , Aortic Valve/pathology , Aortic Valve Disease/genetics , Aortic Valve Disease/pathology , Aortic Valve Stenosis/pathology , Calcinosis/genetics , Calcinosis/pathology , Constriction, Pathologic/genetics , Constriction, Pathologic/pathology , Female , Gene Expression Regulation/genetics , Heart Transplantation/adverse effects , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , RNA-SeqABSTRACT
OBJECTIVE: Endoscopic radial artery (RA) harvesting performed concurrently with internal mammary artery (IMA) takedown and endoscopic saphenous vein (SV) harvesting creates a crowded and inefficient operating room environment. We assessed the effect of a presternotomy RA harvest strategy on surgery time and costs. METHODS: A total of 41 patients underwent elective, first-time, isolated multivessel on-pump coronary artery bypass grafting including an IMA, RA, and SV graft. The first 20 patients (Phase I) underwent endoscopic RA harvesting concurrently with IMA takedown and endoscopic SV harvesting after sternotomy, requiring two sets of endoscopic harvesting equipment per case, each used by a separate individual. The final 21 patients (Phase II) underwent endoscopic RA harvesting during anesthesia line placement, completing the procedure before sternotomy, thus requiring only one set of endoscopic harvesting equipment reused by a single individual. RESULTS: There were no differences in baseline patient characteristics, number of bypasses, duration of SV or RA harvest time, or duration of cardiopulmonary bypass or cross-clamp time between the two groups. Total surgery time was reduced by 32 minutes in Phase II (P = 0.044). Relative to a total hospital direct cost of 100.00 units, total surgery costs were reduced from 29.33 units in Phase I to 25.62 units in Phase II (P = 0.001). No anesthesia- or RA harvest-related complications occurred in either group. CONCLUSIONS: Endoscopic RA harvesting can be safely performed during anesthesia line placement prior to sternotomy. Our simple but innovative strategy improves intraoperative workflow, reduces the time and cost of surgery, and advances the delivery of high-quality patient care.