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

Author(s)

Sharma, Narendra Kumar ^{[1, 2]} ; Ferreira, Bianca Lima ^[1] ; Tashima, Alexandre Keiji ^[3] ; Colo Brunialti, Milena Karina ^[1] ; Soares Torquato, Ricardo Jose ^[3] ; Bafi, Antonio ^[4] ; Assuncao, Murillo ^[5] ; Pontes Azevedo, Luciano Cesar ^[6] ; Salomao, Reinaldo ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Div Infect Dis, Escola Paulista Med, Rua Pedro Toledo, 10th Floor, BR-04039032 Sao Paulo, SP - Brazil

^[2] Banasthali Vidyapith, Dept Biosci & Biotechnol, Banasthali Tonk 304022, Rajasthan - India

^[3] Univ Fed Sao Paulo, Dept Biochem, Escola Paulista Med, BR-04023900 Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo, Hosp Sao Paulo, Escola Paulista Med, Intens Care Unit, BR-04023900 Sao Paulo - Brazil

^[5] Hosp Israelita Albert Einstein, Intens Care Unit, BR-05652900 Sao Paulo - Brazil

^[6] Hosp Sirio Libanes, Intens Care Unit, BR-01409001 Sao Paulo - Brazil

• Document type: Journal article
• Source: CLINICAL PROTEOMICS; v. 16, JUL 16 2019.
• Web of Science Citations: 2

Abstract

BackgroundSepsis 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.MethodsPlasma samples were obtained from patients (n=27) at admission and after 7days 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.ResultsWe identified 159 altered proteins in septic patients; most of them were common when comparing patients' outcomes, both at admission and after 7days. 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.ConclusionProteomic 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. (AU)

• FAPESP's process: 11/20401-4 - Sepsis: integrating basic research and clinical research II
• Grantee: Reinaldo Salomão
• Support Opportunities: Research Projects - Thematic Grants