Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome

BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

Optimal use of fielder XT guidewire enhances the success rate of chronic total occlusion percutaneous coronary intervention

BACKGROUND Chronic total occlusion(CTO) is found in 18-31% of patients who undergo coronary angiography. Successful recanalization of CTOs is associated with reduced recurrent angina pectoris rates and increased long-term survival.Although the success rate of CTO percutaneous coronary intervention(CTO-PCI)has improved, CTO-PCI remains technically challenging. The Fielder XT guidewire was designed for CTO lesions. To validate whether the use of the guidewire increases the success rate, we compared the results of CTO-PCI with or without the guidewire. We hypothesized that the use of Fielder XT guidewire can increase the success rate of CTO-PCI.AIM To investigate whether the use of Fielder XT guidewire increases the final procedural success of CTO-PCI via the anterograde approach.METHODS Between January 2013 and December 2015, a retrospective study was conducted on 1230 consecutive patients with CTO who received PCI via the anterograde approach at the General Hospital of Northern Theater Command. The patients were divided into an XT Group(n = 686) and a no-XT Group(n = 544) depending on whether Fielder XT guidewire was used. Both groups were compared for clinical parameters, lesion-related characteristics, procedural outcomes and inhospital complications. The data were statistically analyzed using Pearson's χ~2 test for categorical variables, and Students' t test was used to compare the quantitative data. Significant independent factors and a risk ratio with 95%confidence interval(CI) were assessed by multivariate logistic regression analysis.RESULTS In total, 1230 patients were recruited; 75.4% of the patients were male, and 55.8%of the patients were in the XT group. The overall success rate was 83.9%, with87.8% in the XT group. Based on multivariate logistic regression analysis, factors positively associated with procedural success were the use of Fielder XT guidewire(P = 0.005, 95%CI: 1.172-2.380) and systolic blood pressure(P = 0.011,95%CI: 1.003-1.022), while factors negatively associated with procedural success were blunt stump(P = 0.013, 95%CI: 1.341-11.862), male sex(P = 0.016, 95%CI:0.363-0.902), New York Heart Association(NYHA) class(P = 0.035, 95%CI: 0.553-0.979), contrast amount(P = 0.018, 95%CI: 0.983-0.998) and occlusion time(P =0.009, 95%CI: 0.994-0.999). No significant differences were found between the XT group and the no-XT group with respect to clinical parameters, lesion-related characteristics, coronary artery rupture [3(0.4%) vs 8(1.5%), P = 0.056], inhospital death [2(0.3%) vs 6(1.1%), P = 0.079] or in-hospital target lesion revascularization [3(0.4%) vs 7(1.3%), P < 0.099]. However, there were significant differences between the groups with respect to success rate [602(87.8%) vs 430(79.0%), P < 0.001], procedure time [(74 ± 23) vs(83 ± 21), P < 0.001], stent length[(32.0 ± 15.8) vs(37.3 ± 17.6), P < 0.001], contrast amount [(148 ± 46) vs(166 ± 43),P < 0.001], post-PCI myocardial infarction [43(6.3%) vs 59(10.8%), P = 0.004],major adverse cardiovascular event [44(6.4%) vs 57(10.7%), P = 0.007], side branch loss [31(4.5%) vs 44(8.1%), P = 0.009], contrast-induced nephropathy [29(4.2%) vs 40(7.4%), P = 0.018] and no reflow [8(1.2%) vs 14(2.9%), P = 0.034].CONCLUSION The use of Fielder XT guidewire shortens the Procedure and increases the success rate of CTO-PCI, and is also associated with reduced complication rates.