Lipid metabolism impairment in patients with sepsis secondary to hospital acquired pneumonia, a proteomic analysis

Abstract

Background Sepsis is a dysregulated host response to infection and a major cause of death worldwide. Respiratory tract infections account for most sepsis cases and depending on the place of acquisition, i.e., community or hospital acquired infection, differ in etiology, antimicrobial resistance and outcomes. Accordingly, the host response may be different in septic patients secondary to community-acquired pneumonia and hospital acquired pneumonia (HAP). Proteomic analysis is a useful approach to evaluate broad alterations in biological pathways that take place during sepsis. Here we evaluated plasma proteome changes in sepsis secondary to HAP. Methods Plasma samples were obtained from patients (n = 27) at admission and after 7 days of follow-up, and were analyzed according to the patients’ outcomes. The patients’ proteome profiles were compared with healthy volunteers (n = 23). Pooled plasma samples were labeled with isobaric tag for relative and absolute quantitationand analyzed by LC–MS/MS. We used bioinformatics tools to find altered functions and pathways. Results were validated using biochemical estimations and ELISA tests. Results We identified 159 altered proteins in septic patients; most of them were common when comparing patients’ outcomes, both at admission and after 7 days. The top altered biological processes were acute inflammatory response, response to wounding, blood coagulation and homeostasis. Lipid metabolism emerged as the main altered function in patients, with HDL as a central node in the network analysis, interacting with downregulated proteins, such as APOA4, APOB, APOC1, APOL1, SAA4 and PON1. Validation tests showed reduced plasma levels of total cholesterol, HDL-C, LDL-C, non-HDL cholesterol, apolipoproteins ApoA1 and ApoB100, and Paraoxonase 1 in HAP patients. Conclusion Proteomic analysis pointed to impairment of lipid metabolism as a major change in septic patients secondary to HAP, which was further validated by the reduced levels of cholesterol moieties and apolipoproteins in plasma. Our results stress the involvement of lipids in the pathogenesis of sepsis, which is in accordance with previous reports supporting the role of lipid moieties in pathogen toxin clearance and in modulating inflammatory responses. Electronic supplementary material The online version of this article (10.1186/s12014-019-9252-2) contains supplementary material, which is available to authorized users.

A Preliminary Study on Blood Lipid Profile in Patients with COVID-19

“…Previous studies have reported that lipid metabolism impairment may be involved in the pathogenesis of sepsis secondary to pneumonia and in uenza [8][9][10]. Similarly, recent studies observed dyslipidemia in patients infected with SARS-CoV-2, using MS analysis [6,7] and routine laboratory lipid tests [11], indicating that blood lipid might involve in the pathogenesis of COVID-19.…”

High-density lipoproteins during sepsis: from bench to bedside

“…Focusing on apolipoproteins, the authors demonstrated a decrease of some apolipoproteins (ApoA-I, ApoA-II, ApoA-IV, ApoB, ApoC-I, ApoC-II, ApoC-III, and ApoE). A recent study on the lipidome showed a decrease in phospholipid concentration in hospital-acquired pneumonia [83].…”

Low serum level of apolipoprotein A1 is an indicator of severity in patients with coronavirus disease 2019

“…Previous studies have found that lipid metabolism impairment may involve in the pathogenesis of sepsis secondly to pneumonia and in uenza [10][11][12]. Similarly, recent studies observed the dyslipidemia in the patients infected with SARS-CoV-2 by MS analysis, especially in the severe cases [7][8][9], which reminded us that blood lipid might serve as a maker for the severity of COVID-19.…”