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- W2029132023 abstract "Aortic injury following trauma results in widespread tissue hypoxia, anaerobic metabolism, and inflammatory cytokines injurious to the vascular endothelium. Previous studies have demonstrated a metabolic protective effect with the administration of Valproic acid (VPA) following traumatic injury. In an effort to identify the gene transcriptional changes, we employed fluorescent microarray analysis to elucidate critical pathways and gene products involved in endothelial cell dysfunction in order to determine the protective mechanism of VPA. A hemorrhage/ischemia-reperfusion (H/I-R) model mimicking the physiologic changes following a ruptured abdominal aortic aneurysm was performed on fifteen Yorkshire swine. This model consisted of 35% hemorrhage, a 50 minute supraceliaic aortic cross clamp, and six hours of full resuscitation divided into three equal groups: a sham group, a H/I-R, and an intervention group receiving VPA at the time of cross clamp application. Aortic endothelium was analyzed by microarray technique and functional clusters were identified through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. Swine in the H/I-R group developed profound acidosis, anemia, and coagulopathy with massive resuscitative fluid requirements and validated histologic injury. These changes were significantly mitigated in swine receiving VPA. In the experimental group, 1,536 gene transcripts (529 up and 1,007 down) underwent significant change. The analysis focused on 232 up regulated genes and 183 down regulated genes that were similar in the VPA intervention and sham groups compared to the H/I-R group. This comparison identified the TGFβ pathway as being critical in endothelial dysfunction and that VPA interacted through this pathway for clinical benefit. TGFβ plays a crucial role in the development of endothelial cell injury and VPA partially mitigates these adverse changes." @default.
- W2029132023 created "2016-06-24" @default.
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- W2029132023 date "2011-06-01" @default.
- W2029132023 modified "2023-10-16" @default.
- W2029132023 title "PVSS14. Norman M. Rich Military Vascular Surgery Presentation - Microarray and Functional Cluster Analysis Implicates Transforming Growth Factor Beta1 in Endothelial Cell Dysfunction and Valproic Acid Benefit in A Swine Hemorrhagic Shock Model" @default.
- W2029132023 doi "https://doi.org/10.1016/j.jvs.2011.03.025" @default.
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