Schillinger Martin, Exner Markus, Mlekusch Wolfgang, Ahmadi Ramazanali, Rumpold Helmut, Mannhalter Christine, Wagner Oswald, Minar Erich
Department of Angiology, University of Vienna Medical School, Vienna, Austria.
J Endovasc Ther. 2002 Aug;9(4):385-94. doi: 10.1177/152660280200900401.
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.
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.
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).
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.
研究具有强大抗炎能力的血红素加氧酶-1(HO-1)基因型与球囊血管成形术诱导的炎症反应之间的关联。
对317例接受股腘球囊血管成形术(n = 150)或支架置入术(n = 61)的患者(188例男性;中位年龄70岁,范围57 - 77岁)进行HO-1基因型上调评估;106例接受下肢血管造影的患者作为对照。在干预后24小时和48小时测量急性期反应物C反应蛋白(CRP)、血清淀粉样蛋白A(SAA)和纤维蛋白原,并与基线值进行比较。评估这些炎症标志物的相对增加量(Δ,%)与HO-1基因启动子中短(<25)(GT)(n)二核苷酸重复序列之间的关联。
球囊血管成形术后,HO-1基因型与ΔCRP(24)(p < 0.0001)、ΔCRP(48)(p < 0.0001)、ΔSAA(24)(p = 0.02)和ΔSAA(48)(p = 0.006)显著相关;Δ纤维蛋白原无关联。球囊血管成形术后ΔCRP(48)较高的患者出现短(<25)(GT)(n)重复序列的几率显著降低。在多变量模型中,ΔCRP(48)值的第三个四分位数的调整后几率降低为80%(p = 0.002),第四个四分位数为90%(p = 0.001)。在支架置入术后24小时和48小时(p = 0.3, p = 0.5)或血管造影术后(p = 0.2, p = 0.6)未发现HO-1基因型与炎症反应之间的关联。
HO-1启动子基因型与球囊血管成形术后出现的炎症反应独立相关。短等位基因(<25 GT重复序列)似乎是一种内在的血管抗炎因子。