METABOLOMIC AND PROTEOMIC CHANGES IN TRAUMA-INDUCED HYPOCALCEMIA.

METABOLOMIC AND PROTEOMIC CHANGES IN TRAUMA-INDUCED HYPOCALCEMIA.
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创伤引起的低钙血症的代谢组和蛋白质组变化。

DOI:
10.1097/shk.0000000000002220
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发表时间:
2023
期刊:
Shock (Augusta, Ga.)
影响因子:
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通讯作者:
D'Alessandr
D'Alessandr
中科院分区:
--
文献类型:
--
作者:
SchaidJr,TerryR;LaCroix,Ian;Cohen,MitchellJ;Hansen,KirkC;Moore,ErnestE;Sauaia,Angela;Cralley,AlexisL;Thielen,Otto;Hallas,William;Erickson,Christopher;Mitra,Sanchayita;Dzieciatkowska,Monika;Silliman,ChristopherC;D'Alessandr

文献摘要

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BackgroundTrauma-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 normocalcemic and hypocalcemic trauma patients to illuminate biochemical pathways that may underlie a distinct pathology linked with this clinical phenomenon.MethodsPlasma 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 before metabolome-and proteome-wide comparisons between normocalcemic (ionized Ca 2+> 1.0 mmol/L) and hypocalcemic (ionized Ca 2+≤ 1.0 mmol/L) patients using partial least squares-discriminant analysis. OmicsNet and Gene Ontology were used for network and pathway analyses, respectively.ResultsExcluding 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 normocalcemic and hypocalcemic patients. Hypocalcemic patients had evidence of mitochondrial dysfunction (tricarboxylic acid cycle disruption, dysfunctional fatty acid oxidation), inflammatory dysregulation (elevated damage-associated molecular patterns, activated endothelial cells), aberrant coagulation pathways, and proteolytic imbalance with increased tissue destruction.ConclusionsIndependent 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.