Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles

Shahan Syed, Eija Nissilä, Hanna Ruhanen, Satoshi Fudo, Meztlli O. Gaytán, Sanna P. Sihvo, Martina B. Lorey, Jari Metso, Katariina Öörni, Samantha J. King, Oommen P. Oommen, Matti Jauhiainen, Seppo Meri, Reijo Käkelä, Karita Haapasalo

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Abstract

High-density lipoproteins (HDLs) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway. Importantly, changes in the protein and lipid composition of HDLs may lead to the formation of particles with reduced atheroprotective properties. Here, we show that Streptococcus pneumoniae pneumolysin (PLY) and neuraminidase A (NanA) impair HDL function by causing chemical and structural modifications of HDLs. The proteomic, lipidomic, cellular, and biochemical analysis revealed that PLY and NanA induce significant changes in sialic acid, protein, and lipid compositions of HDL. The modified HDL particles have reduced cholesterol acceptor potential from activated macrophages, elevated levels of malondialdehyde adducts, and show significantly increased complement activating capacity. These results suggest that accumulation of these modified HDL particles in the arterial intima may present a trigger for complement activation, inflammatory response, and thereby promote atherogenic disease progression.

Original languageEnglish
Article number102535
JournalIscience
Volume24
Issue number6
DOIs
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed

Keywords

  • Cardiovascular medicine
  • Microbiology

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • General

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