ABSTRACT
BACKGROUND: This study evaluated the effect of omeprazole or pantoprazole on platelet reactivity in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients receiving clopidogrel. METHODS: Consecutive patients with NSTE-ACS (n = 620) from general hospital of Shenyang Military Command were randomized to the omeprazole or pantoprazole (20 mg/d) group (1:1), and received routine dual antiplatelet treatment. Patients' reversion rate of adenosine diphosphate-induced platelet aggregation (ADP-PA) was assessed at baseline, 12 to 24 h after administration of medication, and after 72 h of percutaneous coronary intervention (PCI). The primary endpoint of the study was platelet reactivity assessed with ADP-PA at 30 days after PCI. Adverse events (AEs) were recorded for 30-day and 180-day follow-up periods. RESULTS: There were no significant differences between both the groups in platelet response to clopidogrel at 12-24 h after drug administration (54.09% ± 18.90% vs 51.62% ± 19.85%, P = 0.12), 72 h after PCI (52.15% ± 19.45% vs 49.66% ± 20.05%, P = 0.18), and 30 days after PCI (50.44% ± 14.54% vs 48.52% ± 15.08%, P = 0.17). The rate of AEs did not differ significantly between groups during the 30-day (15.2% vs 14.8%, P = 0.91) and 180-day (16.5% vs 14.5%, P = 0.50) follow-up periods after PCI. CONCLUSIONS: The addition of omeprazole or pantoprazole to clopidogrel did not restrict the effect of platelet aggregation by reducing the conversion of clopidogrel. Compared with clopidogrel alone, pantoprazole-clopidogrel and omeprazole-clopidogrel combinations did not increase the incidence of adverse clinical events during 30-day and 180-day follow-up periods after PCI. TRIAL REGISTRATION: The study is registered in the National Institutes of Health website with identifier NCT01735227. Registered 14 November 2012.
ABSTRACT
OBJECTIVE: To investigate the relevant expression of CXCL5 and CXCR2 in human atherosclerotic coronary artery and to study the association between the CXCL5 variant and coronary artery disease (CAD) in a Chinese Han population. MATERIALS AND METHODS: CXCL5 and CXCR2 expression in human coronary arteries was detected by immunohistochemical staining and western blotting analysis. The association between the CXCL5 variant and CAD was determined in a community-based sample by PCR-direct sequence analysis in a Chinese Han population. Finally, plasma CXCL5 levels were measured in a case-control study of CAD patients. RESULTS: We found that CXCL5 and CXCR2 expressions were higher in atherosclerotic coronary arteries plaque than in the normal coronary arteries. CXCL5 and CXCR2 expression levels increased in line with coronary artery lesion stages. A functional nonsynonymous -156 G/C in the CXCL5 promoter region was associated with CAD and plasma CXCL5 levels were significantly increased in CAD patients compared with control subjects (3891.21±1403.08 vs. 2812.39±840.62 pg/ml, P<0.05). Individuals with the CXCL5 promoter -156 G/C variant C/C and G/C carriers had higher plasma CXCL5 levels than those with the G/G genotype carriers in both CAD patients and control participants. CONCLUSION: CXCL5 and CXCR2 are enriched in human atherosclerotic coronary artery. Our findings show that the CXCL5 variant might be a genetic risk factor for the susceptibility of CAD and the CXCL5 promoter -156 G/C C allele might be an independent predictor for CAD. CXCL5 may be a useful molecular marker and a possible target for the treatment of CAD.
Subject(s)
Chemokine CXCL5/genetics , Coronary Artery Disease/genetics , RNA, Messenger/metabolism , Receptors, Interleukin-8B/metabolism , Aged , Alleles , Asian People/genetics , Blotting, Western , Case-Control Studies , Chemokine CXCL5/metabolism , China , Coronary Artery Disease/metabolism , Female , Genetic Predisposition to Disease , Genotype , Humans , Immunohistochemistry , Male , Middle Aged , Polymorphism, Single Nucleotide , Promoter Regions, Genetic/genetics , Proportional Hazards Models , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
The importance of matrix metalloproteinase 8 (MMP8) expression during the progression of thoracic aortic dissection (TAD) has been recently emphasized. Genetic variations that affect proteinase expression or activity might contribute to the pathogenesis of TAD. In this study, we investigated whether the MMP8 C-799T genotype is associated with TAD. The frequency distributions of the MMP8 C-799T polymorphism were determined by direct sequencing. Associations between the polymorphism and disease progression in TAD were investigated. The level of plasma and tissue MMP8 was measured by enzyme-linked immunosorbent assay and western blotting. The MMP8 C-799T polymorphism was significantly associated with susceptibility to disease progression in TAD patients (n = 152) than in controls (n = 147) (P = 0.004, OR = 0.62, 95 % CI 0.45-0.86). The TT homozygotes had a significantly higher risk of TAD compared to C allele carriers in a logistic regression model, after adjustment for the conventional risk factors for TAD. The plasma MMP8 concentration was significantly higher in TAD patients compared to control patients (P < 0.05). TT genotypes had increased MMP8 levels compared to CC and CT genotype carriers in both TAD and control subjects (P < 0.05). The C-799T polymorphism in the MMP8 promoter is part of the genetic variation underlying the susceptibility of individuals to the progression of TAD.
