High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A.
OBJECTIVE
High-density lipoprotein (HDL) is known to have potent anti-inflammatory properties. Monocyte chemoattractant protein-1 is an important pro-inflammatory cytokine in early atherogenesis. There is evidence that HDL can lose its protective function during inflammatory disease. In patients with end-stage renal disease (ESRD), epidemiological studies have documented that the inverse correlation between HDL-cholesterol and cardiovascular risk is lost. Many structural modifications leading to reduced HDL function have been characterized, but the functional consequences are not fully understood.


RESULTS
We showed that HDL from patients with ESRD has a lower anti-inflammatory potential by reduced inhibition of monocyte chemoattractant protein-1 formation in vascular smooth muscle cells. Via a proteomic approach, we identified proteins in HDL from ESRD patients exerting pro-inflammatory actions. By chromatographic separation of proteins and mass-spectrometric analysis, we found serum amyloid A (SAA) to be one molecule acting as a potent pro-inflammatory protein. SAA is enriched in HDL from ESRD patients, correlating with reduced anti-inflammatory capacity. In SAA signal transduction, activation of formyl-peptide receptor 2 is involved. SAA enrichment in HDL of healthy subjects reduced the anti-inflammatory capacity of HDL and correlated with its decreased function.


CONCLUSIONS
These results suggest that SAA enrichment of HDL during disease conditions contributes to the decreased protective function. It is a novel finding that SAA acts as a pro-inflammatory molecule to reduce the anti-inflammatory properties of HDL.
Med. Klinik mit - SP Nephrologie,  Charité - Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin,  Germany.
Markus
M
Tölle
Tao
T
Huang
Mirjam
M
Schuchardt
Vera
V
Jankowski
Nicole
N
Prüfer
Joachim
J
Jankowski
Uwe J F
UJ
Tietge
Walter
W
Zidek
Markus
M
van der Giet
D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005786:Gene Expression Regulation; D005858:Germany; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000276:immunology; D008075:Lipoproteins, HDL / Q000097:blood*; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D000685:Serum Amyloid A Protein