Heme oxygenase-1 genotype is a vascular anti-inflammatory factor following balloon angioplasty.
OBJECTIVE
To investigate the association of the heme oxygenase-1 (HO-1) genotype, which has potent anti-inflammatory capability, and the inflammatory response induced by balloon angioplasty.


METHODS
Three hundred seventeen patients (188 men; median age 70 years, range 57-77) undergoing femoropopliteal balloon angioplasty (n=150) or stenting (n=61) were evaluated for upregulation of the HO-1 genotype; 106 patients undergoing lower limb angiography served as controls. The acute phase reactants C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen were measured 24 and 48 hours postintervention and compared to baseline values. An association of the relative increase (Delta, %) of these inflammatory markers with short (<25) (GT)(n) dinucleotide repeats in the HO-1 gene promoter was assessed.


RESULTS
The HO-1 genotype was significantly associated with Delta CRP(24) (p<0.0001), Delta CRP(48) (p<0.0001), Delta SAA(24) (p=0.02), and Delta SAA(48) (p=0.006) after balloon angioplasty; Delta fibrinogen showed no association. Patients with a higher Delta CRP(48) after balloon angioplasty exhibited significantly reduced odds for the presence of short (<25) (GT)(n) repeats. The adjusted odds reduction in the multivariate model was 80% (p=0.002) in the third quartile of Delta CRP(48) values and 90% (p=0.001) in the fourth quartile. No association of HO-1 genotype and inflammatory response was found 24 and 48 hours after stenting (p=0.3, p=0.5) or angiography (p=0.2, p=0.6).


CONCLUSIONS
The HO-1 promoter genotype is independently associated with the inflammatory response seen after balloon angioplasty. Short alleles (<25 GT repeats) seem to be an intrinsic vascular anti-inflammatory factor.
Schillinger
Martin
M
Department of Angiology, University of Vienna Medical School, Vienna, Austria. martin.schillinger@akh-wien.ac.at
Exner
Markus
M
Mlekusch
Wolfgang
W
Ahmadi
Ramazanali
R
Rumpold
Helmut
H
Mannhalter
Christine
C
Wagner
Oswald
O
Minar
Erich
E
D000368:Aged; D000800:Angioplasty, Balloon; D001053:Apolipoproteins / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D005260:Female; D005263:Femoral Artery; D005340:Fibrinogen / Q000032:analysis; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011150:Popliteal Artery; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D000685:Serum Amyloid A Protein; D015607:Stents; D015854:Up-Regulation
D001053:Apolipoproteins; D008565:Membrane Proteins; D000685:Serum Amyloid A Protein; D005340:Fibrinogen; D002097:C-Reactive Protein; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1