Heat Shock Protein 90 in Severe Trauma

Zhao, Yan; Zhou, Yuanguo

doi:10.1007/978-3-030-23158-3_24

Cited by 1 publication

(1 citation statement)

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“…Elevations in multiple acute phase proteins (serum amyloid A-4 and P-component proteins, complement C4b binding protein alpha chain) were top differentiators of hypocalcemic patients. Heat shock protein 90-b (HSP90b) was also elevated in hypocalcemic patients; activated endothelial cells are a potential source of this stress signal, perhaps as a consequence of Ca 2+ influx, and HSP90b has been found elevated in both sepsis and trauma, associated with endothelial permeability (22,23). Soluble L-selectin was also among the top hypocalcemiadifferentiating proteins that were relatively low in hypocalcemic patients.…”

Section: Inflammatory Dysregulationmentioning

confidence: 99%

Metabolomic and Proteomic Changes in Trauma-induced Hypocalcemia

Schaid,

LaCroix,

Cohen

et al. 2023

Shock

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Background Trauma-induced hypocalcemia is common and associated with adverse outcomes, but the mechanisms remain unclear. Thus, we aimed to characterize the metabolomic and proteomic differences between normo- and hypocalcemic trauma patients to illuminate biochemical pathways that may underlie a distinct pathology linked with this clinical phenomenon. Methods Plasma was obtained on arrival from injured patients at a Level 1 Trauma Center. Samples obtained after transfusion were excluded. Multiple regression was used to adjust the omics data for injury severity and arrival base excess prior to metabolome- and proteome-wide comparisons between normo- (ionized Ca2+ > 1.0 mmol/L) and hypocalcemic (ionized Ca2+ ≤ 1.0 mmol/L) patients using partial least squares-discriminant analysis. OmicsNet and Gene Ontology were used for network and pathway analyses, respectively. Results Excluding isolated traumatic brain injury and penetrating injury, the main analysis included 36 patients (n = 14 hypocalcemic, n = 22 normocalcemic). Adjusted analyses demonstrated distinct metabolomic and proteomic signatures for normo- and hypocalcemic patients. Hypocalcemic patients had evidence of mitochondrial dysfunction (TCA cycle disruption, dysfunctional fatty acid oxidation), inflammatory dysregulation (elevated DAMPs, activated endothelial cells), aberrant coagulation pathways, and proteolytic imbalance with increased tissue destruction. Conclusions Independent of injury severity, hemorrhagic shock, and transfusion, trauma-induced hypocalcemia is associated with early metabolomic and proteomic changes that may reflect unique pathology in hypocalcemic trauma patients. This study paves the way for future experiments to investigate mechanisms, identify intervenable pathways, and refine our management of hypocalcemia in severely injured patients.

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Section: Inflammatory Dysregulationmentioning

confidence: 99%