HDL proteome remodeling associates with COVID-19 severity

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Souza Junior, Douglas Ricardo ; Martins Silva, Amanda Ribeiro ; Rosa-Fernandes, Livia ; Reis, Lorenna Rocha ; Alexandria, Gabrielly ; Bhosale, Santosh D. ; Ghilardi, Fabio de Rose ; Dalcoquio, Talia Falcao ; Bertolin, Adriadne Justi ; Nicolau, Jose Carlos ; Marinho, Claudio R. F. ; Wrenger, Carsten ; Larsen, Martin R. ; Siciliano, Rinaldo Focaccia ; Di Mascio, Paolo ; Palmisano, Giuseppe ; Ronsein, Graziella Eliza

• Document type: Journal article
• Source: JOURNAL OF CLINICAL LIPIDOLOGY; v. 15, n. 6, p. 796-804, NOV-DEC 2021.
• Web of Science Citations: 1

Abstract

Background: Besides the well-accepted role in lipid metabolism, high-density lipoprotein (HDL) also seems to participate in host immune response against infectious diseases. Objective : We used a quantitative proteomic approach to test the hypothesis that alterations in HDL proteome associate with severity of Coronavirus disease 2019 (COVID-19). Methods: Based on clinical criteria, subjects (n = 41) diagnosed with COVID-19 were divided into two groups: a group of subjects presenting mild symptoms and a second group displaying severe symptoms and requiring hospitalization. Using a proteomic approach, we quantified the levels of 29 proteins in HDL particles derived from these subjects. Results: We showed that the levels of serum amyloid A 1 and 2 (SAA1 and SAA2, respectively), pulmonary surfactant-associated protein B (SFTPB), apolipoprotein F (APOF), and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) were increased by more than 50% in hospitalized patients, independently of sex, HDL-C or triglycerides when comparing with subjects presenting only mild symptoms. Altered HDL proteins were able to classify COVID-19 subjects according to the severity of the disease (error rate 4.9%). Moreover, apolipoprotein M (APOM) in HDL was inversely associated with odds of death due to COVID-19 complications (odds ratio {[}OR] per 1-SD increase in APOM was 0.27, with 95% confidence interval {[}CI] of 0.07 to 0.72, P = 0.007). Conclusion: Our results point to a profound inflammatory remodeling of HDL proteome tracking with severity of COVID-19 infection. They also raise the possibility that HDL particles could play an important role in infectious diseases. (c) 2021 National Lipid Association. Published by Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 15/26722-8 - Drug discovery against human infectious diseases
• Grantee: Carsten Wrenger
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/00696-3 - Proteomic as a tool to understand HDL function and composition
• Grantee: Graziella Eliza Ronsein
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/04923-0 - SARS-CoV-2 glycosylation: a blueprint structural insight for understanding COVID-19 pathogenesis
• Grantee: Giuseppe Palmisano
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/25702-4 - Understanding the effects of high density lipoprotein on human macrophages
• Grantee: Douglas Ricardo de Souza Junior
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/07725-1 - Proteomics: a tool to investigate the composition and function of HDL in hyperlipidemia
• Grantee: Amanda Ribeiro Martins da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
• Grantee: Giuseppe Palmisano
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC