Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS.

IF 3.8 2区 医学 Q1 CRITICAL CARE MEDICINE
Yumi Mitsuyama, Hisatake Matsumoto, Fuminori Sugihara, Satoshi Fujimi, Hiroshi Ogura, Jun Oda
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引用次数: 0

Abstract

Background: Acute respiratory distress syndrome (ARDS) remains a significant clinical challenge, and its pathogenesis is not fully understood. Proteomic analyses of plasma and bronchoalveolar lavage fluid (BALF) in patients with ARDS have been performed to uncover diagnostic and prognostic markers, although previous studies have not adequately focused on longitudinal comparison of biomarkers. This study aimed to elucidate the proteomic profiles of patients with ARDS in the acute and subacute phases to better understand the pathophysiological progression of ARDS.

Methods: This was a single-center, prospective, observational study of adult patients with ARDS in whom plasma and BALF samples were collected in the acute and subacute phases of ARDS and comprehensive proteins were identified and analyzed by mass spectrometry.

Results: Plasma and BALF were collected from 21 ARDS patients and plasma from 24 healthy donors, from which 694 plasma proteins and 2017 BALF proteins were analyzed. Processes related to coagulation and complement commonly activated in plasma and BALF were more pronounced in the acute phase than in the subacute phase. In BALF in the acute phase, pathways related to humoral and immune responses were activated, whereas processes related to chaperones and protein folding were suppressed. IPA analysis showed that B cell receptor signaling was most activated, whereas heat shock protein 90 (HSP90) chaperone cycle, protein folding, and other pathways associated with cellular stress responses and proper protein processing were suppressed. The most activated upstream regulator was interferon gamma (IFN-γ) and the most suppressed was notch receptor 1 (NOTCH1).

Conclusions: The proteomics of plasma and BALF from patients with ARDS were compared in both the acute and subacute phases. In BALF in the acute phase, humoral immunity, mainly B-cell receptor signaling, was activated, whereas the HSP90 cycle and protein folding mechanisms were inactivated.

急性呼吸窘迫综合征患者血浆和支气管肺泡灌洗液病理生理的纵向蛋白质组学分析。
背景:急性呼吸窘迫综合征(ARDS)仍然是一个重大的临床挑战,其发病机制尚不完全清楚。尽管之前的研究没有充分关注生物标志物的纵向比较,但已经对ARDS患者的血浆和支气管肺泡灌洗液(BALF)进行了蛋白质组学分析,以发现诊断和预后标志物。本研究旨在阐明急性和亚急性期ARDS患者的蛋白质组学特征,以更好地了解ARDS的病理生理进展。方法:本研究是一项单中心、前瞻性、观察性研究,研究对象为成年ARDS患者,在ARDS急性期和亚急性期采集血浆和BALF样本,并用质谱法鉴定和分析综合蛋白。结果:采集21例ARDS患者血浆和BALF,采集24例健康供者血浆,分析694个血浆蛋白和2017个BALF蛋白。与血浆和BALF中通常激活的凝血和补体相关的过程在急性期比在亚急性期更为明显。在急性期的BALF中,与体液和免疫反应相关的途径被激活,而与伴侣蛋白和蛋白质折叠相关的过程被抑制。IPA分析显示,B细胞受体信号被激活最多,而热休克蛋白90 (HSP90)伴侣周期、蛋白质折叠和其他与细胞应激反应和适当蛋白质加工相关的途径被抑制。激活最多的上游调节因子是干扰素γ (IFN-γ),抑制最多的是notch受体1 (NOTCH1)。结论:比较急性期和亚急性期ARDS患者血浆和半胱氨酸蛋白组学的差异。在急性期的BALF中,体液免疫,主要是b细胞受体信号被激活,而HSP90周期和蛋白质折叠机制被灭活。
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来源期刊
Journal of Intensive Care
Journal of Intensive Care Medicine-Critical Care and Intensive Care Medicine
CiteScore
11.90
自引率
1.40%
发文量
51
审稿时长
15 weeks
期刊介绍: "Journal of Intensive Care" is an open access journal dedicated to the comprehensive coverage of intensive care medicine, providing a platform for the latest research and clinical insights in this critical field. The journal covers a wide range of topics, including intensive and critical care, trauma and surgical intensive care, pediatric intensive care, acute and emergency medicine, perioperative medicine, resuscitation, infection control, and organ dysfunction. Recognizing the importance of cultural diversity in healthcare practices, "Journal of Intensive Care" also encourages submissions that explore and discuss the cultural aspects of intensive care, aiming to promote a more inclusive and culturally sensitive approach to patient care. By fostering a global exchange of knowledge and expertise, the journal contributes to the continuous improvement of intensive care practices worldwide.
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