Abstract 3040: Quantitative Proteomic Analysis Of HDL Shows Apolipoprotein M (ApoM) As A Possible Marker For COVID-19 Mortality

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 44; no. Suppl_1; p. A3040
• Main Authors: Souza Junior, Douglas R, Silva, Amanda R, Fernandes, Lívia R, Palmisano, Giuseppe, Ronsein, Graziella E
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.05.2024
• Subjects: Apolipoproteins; HDL; Proteomics
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/atvb.44.suppl_1.3040

Introduction: High-density lipoprotein (HDL) comprises a heterogeneous group of particles that differ in many aspects, such as density, size, composition and function. The use of mass spectrometry-based proteomics to investigate HDL protein composition has brought some new insights into the field. The qualitative and quantitative HDL proteome is remodeled in different disease states, such as diabetes mellitus, hypercholesterolemia and kidney dysfunction. Beyond its established role in inflammatory and cardiovascular diseases, HDL's involvement in infectious diseases, such as COVID-19, has recently come to light. Here, we investigate the remodeling of HDL proteome in hospitalized and non-hospitalized COVID-19 patients. Hypothesis: We hypothesize HDL proteome is remodeled in infectious diseases and may be a marker and perhaps a predictor of a poor prognosis. Methods: We implemented a robust, global label-free quantification proteomic approach to unravel relative changes in HDL protein composition. We analyzed the proteome of COVID-19 subjects from Brazil categorized in two groups, hospitalized (n=30) and non-hospitalized (n=11). Results: Comparative analysis between hospitalized and non-hospitalized patients revealed a more than 50% increase in relative levels of certain proteins in hospitalized patients, including the inflammatory proteins serum amyloid A1 and A2, as well as pulmonary surfactant-associated protein B. We also observed reductions in the lipid-metabolism related apolipoprotein A2 and phospholipid transfer protein. These findings, independent of sex, triglyceride and HDL-cholesterol, suggest an inflammatory remodeling of the HDL particles. Further analysis of surviving (n=35) and deceased patients (n=6) indicated a negative association between ApoM levels and odds of death due to COVID-19 complications (odds ratio per 1-SD increase in ApoM was 0.27 [0.07 to 0.72], P=0.007). Conclusions: Our results point out HDL remodeling is a marker of COVID-19 severity and ApoM-carried sphingosine-1-phosphate signaling pathway may play a pivotal role in the disease outcome.