Heart failure is associated with impaired anti-inflammatory and antioxidant properties of high-density lipoproteins.
Oxidative stress and inflammation are hallmarks of the heart failure (HF) disease state. In the present study, we investigated the inflammatory/anti-inflammatory characteristics of high-density lipoproteins (HDL) in patients with HF. Ninety-six consecutive patients with systolic HF were followed in an advanced HF center, and 21 healthy subjects were recruited. Plasma was tested for HDL inflammatory index (HII) using a monocyte chemotactic activity assay, with HII >1.0 indicating proinflammatory HDL. We found significantly increased inflammatory properties of HDL in patients with HF (median HII 1.56 vs 0.59 in controls; p <0.0001). Serum amyloid A level was markedly elevated and the activity of paraoxonase-1, an HDL antioxidant enzyme, was significantly reduced in patients versus controls. HDL and albumin from patients with HF contained markedly elevated levels of oxidized products of arachidonic and linoleic acids. HDL function improved when plasma was treated in vitro with 4F, an apolipoprotein A-I mimetic peptide (40% reduction in HII, p <0.0001). There was no correlation found between HII level and ejection fraction or New York Heart Association functional class. In conclusion, HDL function is significantly impaired and oxidation products of arachidonic and linoleic acids are markedly elevated in patients with HF compared with non-HF controls.
Division of Cardiology, Department of Medicine of David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Juyong Brian
JB
Kim
Susan
S
Hama
Greg
G
Hough
Mohamad
M
Navab
Alan M
AM
Fogelman
W Robb
WR
Maclellan
Tamara B
TB
Horwich
Gregg C
GC
Fonarow
D000328:Adult; D000368:Aged; D016718:Arachidonic Acid / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D019787:Linoleic Acid / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D000685:Serum Amyloid A Protein / Q000276:immunology* / Q000378:metabolism
D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein; D016718:Arachidonic Acid; D019787:Linoleic Acid; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human