Hepatocyte growth factor attenuates ischemia/reperfusion induced cardiomyocyte apoptosis via downregulating calcium sensing receptor expression / 中华心血管病杂志

<p><b>OBJECTIVE</b>To examine whether the anti-apoptotic effect of hepatocyte growth factor (HGF) in cardiomyocytes underwent ischemia/reperfusion (I/R) is associated with downregulation of calcium sensing receptor (CaSR) mRNA expression.</p><p><b>METHODS</b>Neonatal rat cardiomyocytes were isolated and randomly divided into 7 groups: control, I/R, GdCl(3), GdCl(3) + NiCl(2) + CdCl(2), GdCl(3) + LY294002, GdCl(3) + HGF, GdCl(3) + HGF + LY294002.I/R was established by incubating primary neonatal rat ventricular cardiomyocytes in ischemia-mimetic solution for 2 h, then reincubated in normal culture medium for 24 h. Cardiomyocyte apoptosis was detected by TUNEL. The expression of CaSR mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of Caspase-3, Bcl-2 and Phosphoinositide-3 Kinase (PI3K) was analyzed by Western blot.</p><p><b>RESULTS</b>I/R enhanced the expression of CaSR mRNA (I/R: 2.62 ± 0.41, control: 1.00 ± 0.31, P < 0.01) and cardiomyocyte apoptosis [I/R: (15.32 ± 2.54)%, control: (2.90 ± 1.45)%, P < 0.01]. GdCl(3) further increased the expression of CaSR mRNA (GdCl(3): 4.46 ± 0.62, I/R: 2.62 ± 0.41, P < 0.01) and cardiomyocyte apoptosis [GdCl(3): (25.36 ± 2.60)%, I/R: (15.32 ± 2.54)%, P < 0.01], along with upregulation of Caspase-3 (GdCl(3): 1.93 ± 0.28, I/R: 1.50 ± 0.21, P < 0.01), downregulation of Bcl-2 (GdCl(3): 0.82 ± 0.18, I/R: 1.71 ± 0.30, P < 0.01) and PI3K phosphorylation inhibition (I/R: 0.87 ± 0.08, GdCl(3): 0.61 ± 0.07, P < 0.01). Combination of GdCl(3) with LY294002 further enhanced cardiomyocytes apoptosis [GdCl(3) + LY294002: (32.6 ± 3.42)%, GdCl(3): (25.36 ± 2.60)%, P < 0.01] but did not affect CaSR mRNA expression (GdCl(3) + LY294002: 4.27 ± 0.56, GdCl(3): 4.46 ± 0.62, P > 0.05). HGF decreased I/R- and GdCl(3)-induced apoptosis [GdCl(3) + HGF: (11.8 ± 1.89)%, GdCl(3): (25.36 ± 2.60)%, P < 0.05] by suppressing Caspase-3 (GdCl(3) + HGF: 1.12 ± 0.23, (GdCl(3): 1.93 ± 0.28, P < 0.05; GdCl(3) + HGF + LY294002: 1.87 ± 0.31, GdCl(3) + LY294002: 3.86 ± 0.47, P < 0.05) and promoting Bcl-2 (GdCl(3) + HGF: 2.56 ± 0.54, GdCl(3): 0.82 ± 0.18, P < 0.05; GdCl(3) + HGF + LY294002: 1.68 ± 0.28, GdCl(3) + LY294002: 0.68 ± 0.13, P < 0.05) and PI3K phosphorylation expression (GdCl(3) + HGF: 2.87 ± 0.21, GdCl(3): 0.61 ± 0.07, P < 0.05; GdCl(3) + HGF + LY294002: 2.01 ± 0.14, GdCl(3) + LY294002: 0.44 ± 0.10, P < 0.05) in accordance with downregulation of CaSR mRNA expression (GdCl(3) + HGF: 1.46 ± 0.37, GdCl(3): 4.46 ± 0.62, P < 0.01).</p><p><b>CONCLUSION</b>HGF exerts protective role in I/R-induced apoptosis at least in part by inhibiting CaSR mRNA expression along with promoting Bcl-2, suppressing Caspase-3 expression and stimulating PI3K phosphorylation signaling pathway.</p>

Clinical study on the coronary artery interventions guided by the magnetic navigation system / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of the magnetic navigation system used in the real world percutaneous coronary artery intervention.</p><p><b>METHODS</b>All lesions detected by the coronary artery angiography in the magnetic-navigation catheter lab indicated for percutaneous coronary artery intervention (PCI) were included and treated under the guidance of the magnetic navigation system. The characteristics of the target lesion, process of the procedure, time and dosage of the X-ray exposure, and procedure-related complication were recorded and analyzed.</p><p><b>RESULTS</b>One hundred and twenty one patients with 138 lesions were recruited and intervened by PCI during the period from April 2006 to June 2008. Thirty lesions were classified as type A, 50 as type B1, 36 as type B2, 22 as type C (including seven total occlusions). The average stenosis of the target lesions was (85.3 +/- 10.0)%, mean length was (21.1 +/- 10.0) mm. Under the guidance of the magnetic navigation system, 134 target lesions were passed by the magnetic guide-wires, the lesion passing ratio was 97.1%. The X-ray exposure time, X-ray dosage and the contrast volume used during the period of the wire placement were (55.9 +/- 35.4) seconds, (98.0 +/- 86.1) mGy/(490.0 +/- 422.2) microGym(2) and (8.0 +/- 5.4) ml, respectively. A total of 164 stents were implanted in the vessels where the target lesions were passed by the magnetic wires. There was no magnetic navigation system associated complication. Magnetic guide-wires failed to pass four target lesions, two of which were chronic total occlusions (CTOs), and the other two were calcified subtotal occlusions.</p><p><b>CONCLUSIONS</b>It is feasible and safe to adopt the magnetic navigation system for the real-world coronary artery intervention. The magnetic guide-wire possesses a high lesion-passing ratio. The CTOs and calcified subtotal occlusions are not ideal lesions for use of the magnetic navigation system.</p>

Effect of genetic polymorphism on the activity of drug transporters and its clinical significance / 中南大学学报(医学版)

Drug transport is an important source of inter-individual variations in drug responses and is also a common site where drug-drug interactions happen. In recent years, more and more novel identified transporters have been added into the transporter super family, and this trend will continue in the future. Among the transporter members of this family, ATP-dependent efflux transporter P-glycoprotein (MDR1) and organic anion transporters (OATP) are the most important proteins involved in drug transport. MDR1 is the most well known transporter. Widely distributed in tissues such as the gastrointestinal tract, liver, kidney and so on, MDR1 plays an important role in drug absorption, distribution and excretion. Its functional genetic polymorphisms have significantly changed the pharmacokinetics of its substrate drugs, which has important clinical implications. OATP expressed in multiple tissues, and it mediated the drug excretion through the bile acid and kidney. Some genetic polymorphism of OATP genes is the cause of some abnormal drug responses.

Effect of intracoronary adenovirus vector encoding hepatocyte growth factor gene on hematopoietic stem cells mobilization in patients with extensive coronary heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of intracoronary adenovirus vector encoding hepatocyte growth factor gene (Ad(5)-HGF) on hematopoietic stem cells mobilization in patients with extensive coronary heart disease.</p><p><b>METHODS</b>Patients with extensive coronary heart disease were treated with intracoronary infusion of adenovirus vector encoding hepatocyte growth factor (Ad(5)-HGF 5 x 10(9) pfu) gene plus stent implantation (n = 9) or equal physiological saline plus stent implantation (n = 9). Angioplasty and stent implantation was performed according to standard clinical practice by the femoral approach and blood samples were drawn from each patient at baseline before PCI, 6 to 24 hours and 6 days post procedure. The number of CD34(+), CD38(+) and CD117(+) cells in peripheral blood was analyzed by flow cytometer.</p><p><b>RESULTS</b>The number of circulating CD34(+) cells in Ad(5)-HGF gene treatment group 6 hours after procedure and the number of circulating CD117(+) cells 6 days post procedure were significantly higher in Ad(5)-HGF gene treatment group than those in the control group (0.104 +/- 0.082 vs. 0.022 +/- 0.012, P = 0.021) and (0.058 +/- 0.058 vs. 0.012 +/- 0.009, P = 0.034), respectively.</p><p><b>CONCLUSION</b>Intracoronary administration of Ad(5)-HGF could mobilize hematopoietic stem cells into peripheral blood and the consequent role of this observation on myocardial regeneration warrants further detailed studies.</p>

Prognostic value of devated baseline C-reactive protein and interleukin-6 levels on the vascular complications in percutaneous coronary intervention / 中华急诊医学杂志

Objective To investigate whether elevated pre-procedural C-reactive protein (CRP) and Interleukin-6 (IL-6) concentrations may be relevant to early outcome in patients undergoing PCI.Method 100 consecutive patients undergoing pereutaneuous coronary intervention (PCI) were included in our study.Peripheral blood samples for CRP and IL-6 testing were withdrawn before PCI.Acute vascular complications resulted from PCI were determined by subsequently coronary angiography.The early coronary events during hospitalization were clinically followed.Results Thirty patients developed acute vessel occlusion,and another one developed subacute coronary thrombosis at 2 days after PCI.Increased levels of CRP correlated well with the occurrence of vascular complications as regards the significant difference existing amongⅠvsⅢandⅠvsⅣquartile groups,P

Effects of nocturnal hypoxemia on carotid artery atherosclerosis and plagues in patients with acute coronary syndrome / 上海第二医科大学学报

0.05).In group Ⅱand Ⅲ,the carotid artery IMT was thicker and the amount of plagues were larger than those in group Ⅰ(P

A study of human annexin V derivative: its effects of anticoagulation and antithrombosis / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of a new anticoagulant, annexin V derivative (AND) on anticoagulation and antithrombosis.</p><p><b>METHODS</b>High and low doses of AND were given to rabbits (groups 1 and 2 respectively) by intravenous (iv) bolus injections followed by half the respective AND doses by iv infusion over 2 hours. Control groups were iv given heparin (group 3) and saline (group 4) of the same volume and procedure as that in group 1 and 2. Blood cell count, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen level were examined before and 15, 30 and 60 min after iv bolus and 2 hours after the end of iv infusion. A 3.0 mm x 15 mm balloon was put into femoral artery to induce endothelial denudation 15 min after IV bolus and the blood pressure of femoral artery was monitored until the pulse pressure recorded 0 mm Hg when the vessel was occluded completely by a thrombus. The femoral arteries were collected and the thrombi were stripped off for measuring their lengths, wet and dry weights.</p><p><b>RESULTS</b>Anticoagulation parameters: APTT at 15 min after iv bolus in AND group was significantly longer than that in group 4 (P < 0.05) but shorter than that in group 3 (P < 0.05); APTT and TT in group 3 were significantly longer than those in groups 1, 2 and 4. Fibrinogen: 0.70 mg/kg AND may decrease fibrinogen. Antithrombosis values: the wet and dry weights in AND groups were significantly lighter than those in group 3 and 4 (P < 0.05). The dry weight in high-dose AND group was remarkably lighter than that in low-dose group (P = 0.029). The length of thrombus in low-dose AND group was remarkably shorter than that in group 4 (P = 0.013), but not for group 3 (P > 0.05). It was remarkably shorter in high-dose AND group than in both group 3 (P < 0.001) and 4 (P = 0.015). The time when pulse pressure equaled to 0 was longer in AND group than in group 4 (P < 0.05), but not in 3.</p><p><b>CONCLUSION</b>AND is an effective anticoagulant and antithrombosis agent, the highest anticoagulation effect occurs at 15 min after IV bolus. Its anticoagulation effect is not more potent than that of standard heparin, while antithrombosis capacity is more effective. AND in treating thrombosis clinically might be promising.</p>