Association between 1019C/T polymorphism of Connexin 37 gene and restenosis after coronary stenting / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between 1019C/T polymorphism of Connexin 37 (CX37) gene and susceptibility to restenosis after percutaneous coronary intervention (PCI) in ethnic Han Chinese patients from Wuxi.</p><p><b>METHODS</b>Five hundred and thirty-two patients with coronary artery disease (CAD) who had undergone PCI underwent coronary angiography (CAG) in 3 months, and were divided into in stent restenosis (ISR) group (n=67) and no instent restenosis (NISR) group (n=465). Five hundred and one healthy individuals have served as the control group. All cases were genotyped with DNA sequencing.</p><p><b>RESULTS</b>Compared with healthy controls, the frequency of CX37 C allele was higher in CAD patients (57.05% vs. 41.32%, P< 0.01). The frequency of C carries (CC+TC) was 79.32% in CAD patients, against 65.47% in healthy controls (P<0.01). The risk for CAD was significantly increased in carriers of C allele (CC+TC) compared with TT homozygotes (OR=2.03, 95% CI: 1.53-2.80). Stratified analysis has indicated a significant difference in the frequency of C allele carriers between both male and female CAD patients and healthy controls (79.63% vs. 72.45%, P=0.02; 78.00% vs. 51.50%, P< 0.01). For both genders, carriers of C allele had a higher risk for CAD compared with TT homozygotes (males: OR=1.48, 95% CI: 1.06-2.09; females: OR=3.34, 95% CI: 1.90-5.86). Compared with NISR group, the frequency of CX37 C allele and C carries (CC+TC) were significantly higher in ISR group (72.39% vs. 54.84%, P< 0.01; 89.55% vs. 77.85%, P=0.027). Compared with TT homozygotes, the risk for restenosis has significantly increased in carriers of C allele (CC+TC) (OR=2.44, 95% CI: 1.08-5.50). Stratified analysis also suggested that the frequency of C carriers was significantly higher in male ISR group compared with male NISR group (92. 86% vs. 77.66%, P=0.008). The risk for restenosis has increased by nearly four fold in carriers of C allele (CC+TC) compared with TT homozygotes (95% CI: 1.32-10.64). However, for female patients, no significant difference was detected in the ISR risk between carriers of CC+TC type and TT homozygotes (P=0.655).</p><p><b>CONCLUSION</b>The C allele of 1019C/T polymorphism in the CX37 gene is associated with susceptibility to CAD as well as restenosis after coronary stenting in male patients from Wuxi.</p>

Molecular mechanisms of diabetic coronary dysfunction due to large conductance Ca2⁺-activated K⁺ channel impairment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca(2+)-activated K(+) (BK) channel activities in coronary dysfunction in streptozotocin-induced diabetic rats.</p><p><b>METHODS</b>Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats.</p><p><b>RESULTS</b>BK currents (defined as the iberiotoxin-sensitive K(+) component) contribute (65 ± 4)% of the total K(+) currents in freshly isolated coronary smooth muscle cells and > 50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca(2+) is impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 (a specific BK channel b(1) subunit activator) robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca(2+) and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 mmol/L Ca(2+). Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-b(1) protein expression in diabetic vessels, without altering the BK channel α-subunit expression. Although the cytosolic Ca(2+) concentration of coronary arterial smooth muscle cells was increased from (103 ± 23) nmol/L (n = 5) of control rats to (193 ± 22) nmol/L (n = 6, P < 0.05) of STZ-induced diabetic rats, reduced BK-b(1) expression made these channels less sensitive to intracellular Ca(2+), which in turn led to enhanced smooth muscle contraction.</p><p><b>CONCLUSIONS</b>Our results indicated that BK channels are the key determinant of coronary arterial tone. Impaired BK channel function in diabetes mellitus is associated with down-regulation of BK-b(1) expression and reduction of the b(1)-mediated BK channel activation in diabetic vessels.</p>

Mechanism related to docosahexaenoic acid induced large conductance calcium-activated potassium channel currents increase in coronary smooth muscle cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of enhanced large conductance calcium-activated potassium channel currents (BK) in coronary smooth muscle cells (SMCs) by docosahexaenoic acid (DHA).</p><p><b>METHODS</b>Coronary SMCs were isolated by enzyme digestion. Potassium channels in coronary SMCs were identified by applications of different potassium blockers. Effects of DHA and its metabolite 16, 17-epoxydocosapentaenoic acid (16, 17-EDP) on BK channels in the absence and presence of cytochrome P450 epoxygenase inhibitor SKF525A were studied by patch clamp in whole-cell configuration.</p><p><b>RESULTS</b>BK channels were widely distributed in SMCs, and BK currents in normal SMCs accounted for (64.2 ± 2.7)% of total potassium currents (n = 20). DHA could activate BK channels, and its 50% effective concentration (EC(50)) was (0.23 ± 0.03) µmol/L, however, the effect of DHA on BK channels was abolished after SMCs were incubated with cytochrome P450 epoxygenase inhibitor SKF525A. 16, 17-EDP, a metabolite of DHA, could reproduce the effects of DHA on BK channels, and its EC(50) was (19.7 ± 2.8) nmol/L.</p><p><b>CONCLUSION</b>DHA and metabolites can activate BK channels and dilate coronary arteries through activating cytochrome P450 epoxygenase pathway.</p>

Value of detecting in-stent restenosis by dual source coronary computed tomography coronary angiography / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the value of dual source computed tomography coronary angiography (DSCT-CA) on detecting in-stent restenosis (> 50% luminal narrowing) in symptomatic patients referred for quantitative coronary angiography (QAC).</p><p><b>METHODS</b>Fifty five patients (43 males) with chest pain after coronary stent implantation within 6 - 12 months were evaluated by DSCT-CA and QAC. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of DSCT-CA were calculated using coronary angiography as gold standard.</p><p><b>RESULTS</b>Eighty nine stents were implanted. In-stent restenosis was evidenced in 28 stents (31.5%) by QAC. The sensitivity, specificity PPV and NPV of DSCT-CA for the diagnosis of in-stent restenosis was 89%, 87%, 76% and 95%, respectively. Diagnostic efficiency was not affected by heart rate and the sensitivity was 0.94 vs. 0.82, the specificity 0.88 vs. 0.90, the PPV 0.76 vs. 0.75 and the NPV 0.97 vs. 0.93 (all P > 0.05) between patients with heart rate < 70 beats/min and patients with heart rate ≥ 70 beats/min. The sensitivity (84% vs. 100%), specificity (81% vs. 96%), PPV (70% vs. 90%) and NPV (91% vs. 100%) were similar between overlapping or bifurcations stents and single stents. The specificity (100% vs. 80% vs. 66%) and PPV (100% vs. 95% vs. 53%) were significantly higher in the groups with stents ≥ 3.50 mm, stents 3.00 mm than in stents ≤ 2.75 mm (both P < 0.05).</p><p><b>CONCLUSION</b>Diagnostic efficiency of in-stent restenosis with DSCT-CA in the large diameter stent is better than in the small diameter stent and the diagnosis efficacy is not affected by heart rate and stent distribution.</p>

Time course of C4a and platelet aggregation rates in no-reflow patients with acute myocardial infarction undergoing percutaneous coronary intervention / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe serum C4a and platelet aggregation rates changes in acute myocardial infarction (AMI) patients before and after percutaneous coronary intervention (PCI) and association with the development of no-reflow phenomenon.</p><p><b>METHODS</b>From June 2006 to August 2009, 119 AMI patients underwent PCI (28 cases of no-reflow group, 91 cases of reflow group) and 30 subjects with suspected coronary heart diseases and normal coronary angiography results (control group) were enrolled in this study. C4a and platelet aggregation rate were measured at 30 minutes before PCI, immediately after PCI, 30 minutes, 1 hour, 2 hour, and 6 months post PCI in AMI patients and at before coronary angiography in control subjects.</p><p><b>RESULTS</b>The levels of serum C4a at 30 minutes prior to PCI in control, no-reflow, and reflow groups were similar (P > 0.05). Platelet aggregation rate at 30 minutes prior to PCI was significantly higher in no-reflow group and reflow group than in control group (all P < 0.05). Serum C4a and platelet aggregation rates were significantly higher in no-reflow group at immediate, 30 minutes and 1 hour after PCI than at 30 minutes prior to PCI, two hours and 6 months after PCI (all P < 0.05), and were significantly higher than in reflow group at immediate, 30 minutes and 1 hour after PCI (all P < 0.05). Serum C4a and platelet aggregation rates were similar at different time points in reflow group (all P > 0.05). The levels of C4a in no-reflow group at immediate, 30 minutes and 1 hour after PCI were positively correlated with platelet aggregation rates (r = 0.91, 0.79, 0.60, respectively, all P < 0.01).</p><p><b>CONCLUSION</b>The transient increase on levels of C4a and platelet aggregation rate early post PCI are verified in no-reflow patients with AMI undergoing PCI.</p>

Changes of large conductance Ca(2+)-activated K(+) channels on coronary smooth muscle cells from diabetic rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the changes of large conductance Ca(2+)-activated K(+) channel (BK channel) on coronary smooth muscle cells from diabetic rats.</p><p><b>METHODS</b>Streptozotocin-induced rat diabetic animal model was used. Coronary smooth muscle cells were isolated by enzyme digestion. BK currents in control and diabetic groups were recorded by patch clamp technique in whole cell configuration, and BK channel protein expression was detected by Western blot. Calcium concentration was measured by fluorescence assay.</p><p><b>RESULTS</b>Compared with control group, BK current densities in diabetic group were significantly decreased when test potentials > 100 mV (P < 0.05). BK current densities were (275 ± 40) pA/pF in control group (n = 8) and (70 ± 10) pA/pF in diabetic group (n = 6) at 150 mV test potentials. α-subunit protein expression was similar between the groups (P > 0.05), however, β1-subunit protein expression was significantly reduced in diabetic group than in control group (P < 0.05). Calcium concentrations were significantly increased in diabetic group control group (151 ± 18) nmol/L (n = 6) than in control group (92 ± 7) nmol/L (n = 5, P < 0.05).</p><p><b>CONCLUSION</b>Observed β1-subunit downregulation, BK current density decrease and cytosolic calcium concentration increase in smooth muscle cells of diabetic coronary arteries may be associated with coronary dysfunction in diabetic rats.</p>