A Weak Response to Endoplasmic Reticulum Stress Is Associated With Postoperative Organ Failure in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

Frontiers in Medicine

article

Thomas Clavier¹  Fabienne Tamion³  Zoé Demailly¹  Xavier Semaille¹  Caroline Thill⁴  Jean Selim¹  Benoit Veber¹  Fabien Doguet²  Vincent Richard²  Emmanuel Besnier¹ 

[1] Rouen University Hospital, Department of Anesthesiology and Critical Care;Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF;Rouen University Hospital, Department of Medical Critical Care;Rouen University Hospital, Department of Biostatistics;Rouen University Hospital, Department of Cardiac Surgery

关键词: bypass;    cardiopulmonary;    cardiac surgery;    endoplasmic reticulum stress;    endothelium;    inflammation;    GRP78 protein;    human;   

DOI  :  10.3389/fmed.2020.613518

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Introduction: Endoplasmic reticulum stress (ERS) is involved in inflammatory organ failure. Our objective was to describe ERS, its unfolded protein response (UPR) expression/kinetics during cardiac surgery with cardiopulmonary bypass (CPB) and its association with postoperative organ failure (OF). Methods: Prospective study conducted on patients undergoing cardiac surgery with CPB. Blood samples were taken before (Pre-CPB), 2 h (H2-CPB) and 24 h (H24-CPB) after CPB. Plasma levels of 78 kDa Glucose- Regulated Protein (GRP78, final effector of UPR) were evaluated by ELISA. The expression of genes coding for key elements of UPR ( ATF6, ATF4, sXBP1, CHOP ) was evaluated by quantitative PCR performed on total blood. OF was defined as invasive mechanical ventilation and/or acute kidney injury and/or hemodynamic failure requiring catecholamines. Results: We included 46 patients, GRP78 was decreased at H2-CPB [1,328 (878–1,730) ng/ml vs. 2,348 (1,655–3,730) ng/ml Pre-CPB; p < 0.001] but returned to basal levels at H24-CPB [2,068 (1,436–3,005) ng/ml]. The genes involved in UPR had increased expression at H2 and H24. GRP78 plasma levels in patients with OF at H24-CPB ( n = 10) remained below Pre-CPB levels [−27.6 (−51.5; −24.2)%] compared to patients without OF ( n = 36) in whom GRP78 levels returned to basal levels [0.6 (−28.1; 26.6)%; p < 0.01]. H24-CPB ATF6 and CHOP expressions were lower in patients with OF than in patients without OF [2.3 (1.3–3.1) vs. 3.0 (2.7–3.7), p < 0.05 and 1.3 (0.9–2.0) vs. 2.2 (1.7–2.9), p < 0.05, respectively]. Conclusions: Low relative levels of GRP78 and weak UPR gene expression appeared associated with postoperative OF. Further studies are needed to understand ERS implication during acute organ failure in humans.

【 授权许可】

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