PMID- 30833653
OWN - NLM
STAT- MEDLINE
DCOM- 20200921
LR  - 20200921
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Mar 4
TI  - Dysfunctional high-density lipoprotein activates toll-like receptors via serum 
      amyloid A in vascular smooth muscle cells.
PG  - 3421
LID - 10.1038/s41598-019-39846-3 [doi]
LID - 3421
AB  - Serum amyloid A (SAA) is an uremic toxin and acute phase protein. It accumulates 
      under inflammatory conditions associated with high cardiovascular morbidity and 
      mortality in patients with sepsis or end-stage renal disease (ESRD). SAA is an 
      apolipoprotein of the high-density lipoprotein (HDL). SAA accumulation turns HDL 
      from an anti-inflammatory to a pro-inflammatory particle. SAA activates monocyte 
      chemoattractant protein-1 (MCP-1) in vascular smooth muscle cells. However, the 
      SAA receptor-mediated signaling pathway in vascular cells is poorly understood. 
      Therefore, the SAA-mediated signaling pathway for MCP-1 production was 
      investigated in this study. The SAA-induced MCP-1 production is dependent on the 
      activation of TLR2 and TLR4 as determined by studies with specific receptor 
      antagonists and agonists or siRNA approach. Experiments were confirmed in tissues 
      from TLR2 knockout, TLR4 deficient and TLR2 knock-out/TLR4 deficient mice. The 
      intracellular signaling pathway is IkappaBalpha and subsequently NFkappaB dependent. The 
      MCP-1 production induced by SAA-enriched HDL and HDL isolated from septic 
      patients with high SAA content is also TLR2 and TLR4 dependent. Taken together, 
      the TLR2 and TLR4 receptors are functional SAA receptors mediating MCP-1 release. 
      Furthermore, the TLR2 and TLR4 are receptors for dysfunctional HDL. These results 
      give a further inside in SAA as uremic toxin involved in uremia-related 
      pro-inflammatory response in the vascular wall.
FAU - Schuchardt, Mirjam
AU  - Schuchardt M
AD  - Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat 
      Berlin, Humboldt Universitat zu Berlin, and Berlin Institute of Health, 
      Department of Nephrology, Hindenburgdamm 30, 12203, Berlin, Germany.
FAU - Prufer, Nicole
AU  - Prufer N
AD  - Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat 
      Berlin, Humboldt Universitat zu Berlin, and Berlin Institute of Health, 
      Department of Nephrology, Hindenburgdamm 30, 12203, Berlin, Germany.
FAU - Tu, Yuexing
AU  - Tu Y
AD  - Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat 
      Berlin, Humboldt Universitat zu Berlin, and Berlin Institute of Health, 
      Department of Nephrology, Hindenburgdamm 30, 12203, Berlin, Germany.
AD  - Zhejiang Provincial People s Hospital, Intensive Care Unit, Hangzhou, China.
FAU - Herrmann, Jaqueline
AU  - Herrmann J
AD  - Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat 
      Berlin, Humboldt Universitat zu Berlin, and Berlin Institute of Health, 
      Department of Nephrology, Hindenburgdamm 30, 12203, Berlin, Germany.
FAU - Hu, Xiu-Ping
AU  - Hu XP
AD  - Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat 
      Berlin, Humboldt Universitat zu Berlin, and Berlin Institute of Health, 
      Department of Nephrology, Hindenburgdamm 30, 12203, Berlin, Germany.
FAU - Chebli, Sarah
AU  - Chebli S
AD  - Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat 
      Berlin, Humboldt Universitat zu Berlin, and Berlin Institute of Health, 
      Department of Nephrology, Hindenburgdamm 30, 12203, Berlin, Germany.
FAU - Dahlke, Katja
AU  - Dahlke K
AD  - Deutsches Institut fur Ernaehrungsforschung, Department of Gastrointestinal 
      Microbiology, Arthur-Scheunert-Allee 114-116, 14558, Nuthethal, Germany.
FAU - Zidek, Walter
AU  - Zidek W
AD  - Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat 
      Berlin, Humboldt Universitat zu Berlin, and Berlin Institute of Health, 
      Department of Nephrology, Hindenburgdamm 30, 12203, Berlin, Germany.
FAU - van der Giet, Markus
AU  - van der Giet M
AD  - Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat 
      Berlin, Humboldt Universitat zu Berlin, and Berlin Institute of Health, 
      Department of Nephrology, Hindenburgdamm 30, 12203, Berlin, Germany. 
      Markus.vanderGiet@charite.de.
FAU - Tolle, Markus
AU  - Tolle M
AD  - Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat 
      Berlin, Humboldt Universitat zu Berlin, and Berlin Institute of Health, 
      Department of Nephrology, Hindenburgdamm 30, 12203, Berlin, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190304
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Serum Amyloid A Protein)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Humans
MH  - Lipoproteins, HDL/*metabolism
MH  - Mice
MH  - Muscle, Smooth, Vascular/*cytology
MH  - Myocytes, Smooth Muscle/*metabolism
MH  - Rats
MH  - Serum Amyloid A Protein/*metabolism
MH  - Toll-Like Receptor 2/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Toll-Like Receptors/*metabolism
PMC - PMC6399289
COIS- The authors declare no competing interests.
EDAT- 2019/03/06 06:00
MHDA- 2020/09/22 06:00
PMCR- 2019/03/04
CRDT- 2019/03/06 06:00
PHST- 2017/03/06 00:00 [received]
PHST- 2019/02/01 00:00 [accepted]
PHST- 2019/03/06 06:00 [entrez]
PHST- 2019/03/06 06:00 [pubmed]
PHST- 2020/09/22 06:00 [medline]
PHST- 2019/03/04 00:00 [pmc-release]
AID - 10.1038/s41598-019-39846-3 [pii]
AID - 39846 [pii]
AID - 10.1038/s41598-019-39846-3 [doi]
PST - epublish
SO  - Sci Rep. 2019 Mar 4;9(1):3421. doi: 10.1038/s41598-019-39846-3.