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

doi:10.1016/j.isci.2021.102535

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^*

^*Tämän työn vastaava kirjoittaja

Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

7 Sitaatiot (Scopus)

14 Lataukset (Pure)

Abstrakti

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.

Alkuperäiskieli	Englanti
Artikkeli	102535
Julkaisu	iScience
Vuosikerta	24
Numero	6
DOI - pysyväislinkit	https://doi.org/10.1016/j.isci.2021.102535
Tila	Julkaistu - 2021
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

This study was supported by the Jane and Aatos Erkko Foundation , Finnish Society for Cardiovascular Diseases , Academy of Finland , and Aarne and Aili Turunen Foundation . Open access funded by Helsinki University Library. This study was supported by the Jane and Aatos Erkko Foundation, Finnish Society for Cardiovascular Diseases, Academy of Finland, and Aarne and Aili Turunen Foundation. Open access funded by Helsinki University Library. All authors edited and approved the final version of the manuscript. S.S. and K.H. wrote the paper; S.S. K.H. E.N. S.F. and M.B.L. performed and analyzed experiments; H.R. S.P.S. and R.K. performed mass spectrometric analyses of lipids; S.J.K. S.M. J.M. M.O.G. M.J. K.?. and O.P.O. provided analytical tools; K.H. designed and supervised the work. The authors declare no competing interests.

Julkaisufoorumi-taso

Jufo-taso 1

!!ASJC Scopus subject areas

General

Pääsy asiakirjaan

10.1016/j.isci.2021.102535

1-s2.0-S2589004221005034-main
CC BY
Final published version, 4,21 MBLisenssi: CC BY

http://urn.fi/URN:NBN:fi:tuni-202106145873Lisenssi: CC BY

Siteeraa tätä

Syed, S., Nissilä, E., Ruhanen, H., Fudo, S., Gaytán, M. O., Sihvo, S. P., Lorey, M. B., Metso, J., Öörni, K., King, S. J., Oommen, O. P., Jauhiainen, M., Meri, S., Käkelä, R., & Haapasalo, K. (2021). Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles. iScience, 24(6), Artikkeli 102535. https://doi.org/10.1016/j.isci.2021.102535

@article{4b13692c71bf4289835ab83ce563d58e,

title = "Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles",

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.",

keywords = "Cardiovascular medicine, Microbiology",

author = "Shahan Syed and Eija Nissil{\"a} and Hanna Ruhanen and Satoshi Fudo and Gayt{\'a}n, \{Meztlli O.\} and Sihvo, \{Sanna P.\} and Lorey, \{Martina B.\} and Jari Metso and Katariina {\"O}{\"o}rni and King, \{Samantha J.\} and Oommen, \{Oommen P.\} and Matti Jauhiainen and Seppo Meri and Reijo K{\"a}kel{\"a} and Karita Haapasalo",

note = "Funding Information: This study was supported by the Jane and Aatos Erkko Foundation , Finnish Society for Cardiovascular Diseases , Academy of Finland , and Aarne and Aili Turunen Foundation . Open access funded by Helsinki University Library. Funding Information: This study was supported by the Jane and Aatos Erkko Foundation, Finnish Society for Cardiovascular Diseases, Academy of Finland, and Aarne and Aili Turunen Foundation. Open access funded by Helsinki University Library. All authors edited and approved the final version of the manuscript. S.S. and K.H. wrote the paper; S.S. K.H. E.N. S.F. and M.B.L. performed and analyzed experiments; H.R. S.P.S. and R.K. performed mass spectrometric analyses of lipids; S.J.K. S.M. J.M. M.O.G. M.J. K.?. and O.P.O. provided analytical tools; K.H. designed and supervised the work. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

doi = "10.1016/j.isci.2021.102535",

language = "English",

volume = "24",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier",

number = "6",

}

Syed, S, Nissilä, E, Ruhanen, H, Fudo, S, Gaytán, MO, Sihvo, SP, Lorey, MB, Metso, J, Öörni, K, King, SJ, Oommen, OP, Jauhiainen, M, Meri, S, Käkelä, R & Haapasalo, K 2021, 'Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles', iScience, Vuosikerta 24, Nro 6, 102535. https://doi.org/10.1016/j.isci.2021.102535

TY - JOUR

T1 - Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles

AU - Syed, Shahan

AU - Nissilä, Eija

AU - Ruhanen, Hanna

AU - Fudo, Satoshi

AU - Gaytán, Meztlli O.

AU - Sihvo, Sanna P.

AU - Lorey, Martina B.

AU - Metso, Jari

AU - Öörni, Katariina

AU - King, Samantha J.

AU - Oommen, Oommen P.

AU - Jauhiainen, Matti

AU - Meri, Seppo

AU - Käkelä, Reijo

AU - Haapasalo, Karita

N1 - Funding Information: This study was supported by the Jane and Aatos Erkko Foundation , Finnish Society for Cardiovascular Diseases , Academy of Finland , and Aarne and Aili Turunen Foundation . Open access funded by Helsinki University Library. Funding Information: This study was supported by the Jane and Aatos Erkko Foundation, Finnish Society for Cardiovascular Diseases, Academy of Finland, and Aarne and Aili Turunen Foundation. Open access funded by Helsinki University Library. All authors edited and approved the final version of the manuscript. S.S. and K.H. wrote the paper; S.S. K.H. E.N. S.F. and M.B.L. performed and analyzed experiments; H.R. S.P.S. and R.K. performed mass spectrometric analyses of lipids; S.J.K. S.M. J.M. M.O.G. M.J. K.?. and O.P.O. provided analytical tools; K.H. designed and supervised the work. The authors declare no competing interests. Publisher Copyright: © 2021 The Author(s)

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Cardiovascular medicine

KW - Microbiology

U2 - 10.1016/j.isci.2021.102535

DO - 10.1016/j.isci.2021.102535

M3 - Article

AN - SCOPUS:85106583779

SN - 2589-0042

VL - 24

JO - iScience

JF - iScience

IS - 6

M1 - 102535

ER -

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

Abstrakti

Rahoitus

Julkaisufoorumi-taso

!!ASJC Scopus subject areas

Pääsy asiakirjaan

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