Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the –607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affili-ated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in is-chemic cerebrovascular disease patients compared with healthy controls. Analysis of the –607C/A (rs1946518) polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C alleles than healthy controls. Genotype and allele frequencies of the interleukin-18 –137G/C (rs187238) polymorphism and the –13T/C (rs11024595) polymorphism in the 5'-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hyper-tension, diabetes mellitus, hypercholesteremia, and an ischemic stroke family history, showed is-chemic cerebrovascular disease risk in individuals without the A allele (C homozygotes) was 2.2-fold greater than in A allele carriers. Overall, our findings suggest that the –13T/C (rs11024595) polymorphism in the 5′-flanking region of serum amyloid A has no correlation with ischemic cere-brovascular disease, but the C allele of the –607C/A (rs1946518) polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A allele is likely a protective gene for ischemic cerebrovascular disease.
Background: Pulmonary ischemia–reperfusion (IR) is a biopathological event detectable in several clinical conditions, including lung transplantation, cardiopulmonary bypass, resuscitation, and pulmonary embolism. The understanding behind the activation of various inflammatory mediators regulating the apoptotic pathways remains largely unknown. We investigated the temporal expression of endothelial nitric oxide (eNOS), inducible (iNOS), and cyclooxygenase-2 (COX-2) proteins following lung-IR injury. Methods: Lung IR was induced in anesthetized rats. One hour ischemia was performed by clamping the left hilum. eNOS, iNOS, and COX-2 levels in the bronchoalveolar lavage (BAL) were measured at different time points after restoring lung perfusion in conjunction with histological changes and cellular apoptosis. Results: BAL-eNOS levels were increased as early as 3 hours post IR, attaining the highest values (5.5 U/mL) at 3 hours, compared to non-IR values (2.8 U/mL). BAL-iNOS increased at 3-hour post-IR (3 U/mL). iNOS reached the highest levels at 24 hours (4.5 U/mL) as compared to nonischemic lungs (1.8 U/mL). COX-2 peaked at 12 hours (.025 U/mL) compared to 3, 24, and 48 hours. Highest apoptotic rates were detected at 12 and 48 hours following IR. Conclusions: The time-associated involvement of eNOS, iNOS, and COX-2 enzymes during the evolution of IR injury may point to an early reaction of the NOSs system versus the COX-2. Similar patterns of enzymatic activity were previously shown in the context of lung IR injury. This temporal activation may indicate an involvement of eNOS in an early reparative response, and possibly the late-pathological response, mediated by the coinduction of iNOS–COX-2.