Effects of tumor necrosis factor alpha on expression of phospholamban and intracellular calcium in cardiomyocytes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effects of tumor necrosis factor alpha (TNFalpha) on the expression of phospholamban (PLB) and sarco (endo) plasmic reticulum Ca(2+)-ATPase (SERCA2a) and concentration of intracellular free calcium in myocardiocytes.</p><p><b>METHODS</b>The neonatal rat myocardiocytes were randomly divided into 6 groups: treatment with different concentrations of TNFalpha (1,10,30,50,and 70 microg/L, respectively) and without TNFalpha (control). The mRNA and protein expression of PLB and SERCA2a were detected with one-step reverse transcription-polymerase chain reaction and Western blotting. The changes of intracellular free calcium concentration ([Ca2+]i) in cultured single neonatal rat cardiomyocyte were determined with Fluo-3/AM loading by laser scanning confocal microscopy. RESULTS TNFalpha significantly increased the expression of PLB mRNA and protein in a dose-dependent fashion. The ratio of PLB/beta-actin mRNA in myocardiocytes incubated with 10,30,50, and 70 microg/L TNFalpha significantly increased by 66%, 106%, 141%, and 189% compared with control (P < 0.05), and protein levels significantly increased by 30%, 48%, 73%, and 114% respectively compared with control (P < 0.001), but there was no significant difference in PLB mRNA expression between the group treated with 1 microg/L TNFalpha and control group. TNFalpha had no effect on the expression of mRNA and protein of SERCA2a. TNFalpha (50 microg/L) incubated with cell for 24 hours diminished delta[Ca2+]i of single neonatal rat cardiomyocyte about 33% stimulated by isoproterenol (P < 0.01), but had no effect on delta [Ca2+]i of cardiomyocyte without isoproterenol stimulation.</p><p><b>CONCLUSION</b>TNFalpha can increase the expression of PLB and decrease delta[Ca2+]i in cardiomyocytes, which may be related with its negative inotropic effects on cardiomyocytes.</p>

Combined effects of ramipril and angiotensin II receptor blocker TCV116 on rat congestive heart failure after myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin converting-enzyme inhibitor (ACEI) is the cornerstone in its treatment. However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin II (Ang II) by alternative pathways. The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang II type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI).</p><p><b>METHODS</b>Congestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery. The experiment protocol included sham-operated rats (Sham), MI-control rats (MI-control), MI rats treated with ramipril 3 mg/kg (MI-ramipril) or TCV116 2 mg/kg (MI-TCV116) per day, half dosage (MI-1/2R&T) or full dosage (MI-R&T) combination of the two. At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as beta myosin heavy chain (betaMHC), B-type natriuretic peptide (BNP), transforming growth factor-beta1 (TGF-beta1), collagen I and III were quantified with reverse transcription polymerase chain reaction (RT-PCR) in the surviving septum myocardium, and survival rates were calculated.</p><p><b>RESULTS</b>There were no significant differences in MI sizes (%) among each MI related experimental groups (33 +/- 13, 34 +/- 14, 33 +/- 13, 35 +/- 13 and 33 +/- 14 for MI-control, MI-ramipril, MI-TCV116, MI-1/2R&T and MI-R&T, respectively, no statistical significance for all). Compared with sham-operated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P < 0.01); while their hemodynamic parameters were significantly impaired (P < 0.01), and in terms of spontaneous deaths survival rate shortened (P < 0.05). Compared with MI rats without therapy, MI rats treated with each single drug showed significant attenuation of mRNA expressions of cardiac molecule genes (P < 0.01); while their hemodynamic parameters were significantly improved (P < 0.05 or P < 0.01), and in terms of spontaneous deaths survival rate prolonged (P < 0.05). Both half and full dosage combined treatments exerted more powerful effects on improvement of cardiac phenotypic changes and on attenuation of betaMHC, BNP mRNA expressions (P < 0.05 vs monotherapy); while LVEDP was further lowered (P < 0.05 vs monotherapy). However, the total death in MI rats with full dosage combined treatment was more though there were no significant differences when compared with other treatments.</p><p><b>CONCLUSIONS</b>The results suggest that treatment with appropriate dosage combination of a chronic ACEI and a chronic ARB may further improve cardiac remodeling and cardiac function after MI.</p>

Effect of tongxinluo capsule on function of vascular endothelium in patients with unstable angina pectoris / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Tongxinluo (TXL) Capsule on function of vascular endothelium in patients with unstable angina pectoris (UAP).</p><p><b>METHODS</b>Forty-six UAP patients were randomly divided into two group, the 28 patients in the treated group treated by conventional therapy plus TXL and the 18 patients in the control group treated by conventional therapy alone. Changes of blood levels of endothelin (ET), nitric oxide (NO), Von Willebrand factor (vWF), soluble vascular cell adhesive molecule-1 (sVCAM-1) and soluble intracellular adhesive molecule-1 (sICAM-1) from before treatment to after two months of treatment were observed, and the flow-mediated dilatation (FMD) in brachial artery was detected at the same time using ultrasonography.</p><p><b>RESULTS</b>After treatment, the blood level of vWF and ET obviously decreased (P < 0.01), levels of NO and FMD increased (P < 0.05 or P < 0.01) in both groups. Levels of sVCAM-1 and sICAM-1 significantly decreased in the treated group (P < 0.01), while in the control group, no marked change was found in sVCAM-1 and sICAM-1 (P > 0.05). Compared with the control group after treatment, the levels of vWF, ET, sVCAM-1 and sICAM-1 in the treated group were lower (P < 0.01), and levels of NO and FMD were higher (P < 0.01).</p><p><b>CONCLUSION</b>TXL might protect vascular endothelium, improve clinical therapeutic effect by path of decreasing blood levels of ET, vWF and partial cellular adhesive factor, and increasing the level of NO.</p>

Experimental study on the relationship between insulin and hypertension / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the association between insulin and hypertension.</p><p><b>METHODS</b>Twenty spontaneously hypertension rats(SHR) and twenty Wistar-Kyoto rats(WKY) were randomly divided into two groups control group and insulin injection group. Systolic blood pressure(SBP),pulse rate(P), fasting blood sugar(FBS), fasting serum insulin(FINS) and insulin sensitivity index(ISI) were observed or calculated before and at the 60th day of the experiment.</p><p><b>RESULTS</b>(SBP 165.5+/-5.8 compared with 108.2+/-4.7mmHg,P<0.01), P(405.8+/-19.6 compared with 336.6+/-9.6 /min P<0.01), FINS (6.89+/-0.99 compared with 5.78+/-0.91mU/L,P<0.05)of SHR were higher than those of WKY before experiment, but there was a lower ISI of SHR -3.397+/-0.191 compared with -3.085+/-0.132,P<0.01 . There were increases of SBP(210.0+/-8.5 compared with 184.3+/-8.0 mmHg,P<0.01),P(452.2+/-13.9 compared with 406.0+/-22.7/min P<0.01) and FINS (28.37+/-3.86 compared with 7.32+/-0.87 mU/L,P<0.01) in insulin injection group of SHR than those in controls,but ISI -4.119+/-0.260 compared with -3.604+/-0.174 P<0.01 decreased in insulin injection group; The same changes were observed in WKY rats after insulin injection (131.6+/-6.7 compared with 110.4+/-5.1 mmHg, 378.2+/-13.2 compared with 347.1+/-14.9/min 22.64+/-2.13 compared with 5.55+/-0.77 mU/L,-3.474+/-0.214 compared with 3.094+/-0.191 P<0.01 respectively).</p><p><b>CONCLUSION</b>Insulin resistance and hyperinsulinemia exist in SHR,chronic hyperinsulinemia may increase SBP and P,decrease ISI of WKY and SHR.</p>

Protective effect of trimetazidine on rabbit myocardium during ischemia- reperfusion / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the protective effects of trimetazidine on rabbit myocardium in ischemia and reperfusion.</p><p><b>METHODS</b>Fourty rabbits were divided into five groups randomly: normal control group, ischemia control group, ischemia and drug intervention group, reperfusion control group, reperfusion and drug intervention group. Ischemia lasted for 30 minutes and reperfusion was given for 30 minutes. Serum CPK, SOD activities and MDA concentrations were measured in each group and ischemia tissue ATP concentrations were also measured. Heart tissue was examined with electron microscope in each group.</p><p><b>RESULTS</b>(1) Serum concentrations of MDA in ischemia and drug intervention group were significantly different from those in ischemia control group [(4.09+/-0.40 vs 4.79+/-0.92)nmol/ml, P<0.01], serum activities of CPK [(1322+/-1148 vs 1498+/-190) NU/ml], SOD[(324+/-71 vs 288+/-54)NU/ml] were not significantly different between ischemia and drug intervene group and ischemic control group (PP>0.05,respectively). (2) Serum activities of CPK [(1512+/-226 vs 1904+/-203) NU/ml], SOD[(213+/-71 vs 119+/-55) NU/ml], concentrations of MDA [(6.09+/-0.69 vs 7.43+/-0.20)nmol/ml] and concentrations of ATP[(1.401+/-0.248 vs 0.629+/-0.175) micromol/g] in ischemia heart tissue of reperfusion and drug intervention group were significantly different from those in reperfusion control group (P<0.001 - 0.01 respectively). (3) There were significant differences in electron microscopic observation between intervention group and control group.</p><p><b>CONCLUSION</b>Trimetazidine can improve cardiac mitochondrial metabolism and scavenge oxygen free radicals. Trimetazidine has cardioprotective function during ischemia and reperfusion.</p>

intercellular adhesion molecule-1 and CD11a/CD18 expression in coronary heart disease / 浙江大学学报·医学版

OBJECTIVE: To investigate the expression of soluble intercellular adhesion molecule-1(sICAM-1) and CD11a/CD18 in coronary heart disease(CHD). METHODS: The sICAM-1 and CD11a/CD18 levels were measured by ELISA and flow cytlemetry in 76 CHD patients and 65 healthy subjects. RESULTS: The level of sICAM-1 and CD11a/CD18 were significantly higher in CHD patients than healthy subjects [SICAM-1(g/L):263.5 +/-66.2 compared with 205.9 +/-57.2, P<0.01; CD11a/CD18 (%):33.7 +/-6.4 compared with 19.3 +/-8.1, P<0.001]. They were also significantly higher in acute myocardial infarct and unstable angina than that of stable angina patients. There was correlation between sICAM-1 and CD11a/CD18(r=0.436, P<0.01). CONCLUSION: Elevated levels of sICAM-1 and CD11a/CD18 associated with unstable angina and myocardial infarction may indicate their significant role in the pathogenesis of acute coronary events.

Angiotensin II increases the expression of lectin-like oxidize low-density lipoprotein receptor- 1 in cultured human umbilical vein endothlial cells / 浙江大学学报·医学版

OBJECTIVE: To observe whether angiotensin II (AngII) influences expression of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) in cultured human umbilical vein endothlial cells(HUVECs). METHODS: Cultured HUVECs were incubated with 10(-5)mol/L approximate, equals 10(-10) mol/L AngII for 24 h or with 10(-6) mol/L AngII for various time up to 48 h. Then HUVECs LOX-1 protein expression was measured by endothlial cell enzyme linked immunosorbent assay, and mRNA level of LOX-1 was detected by quantitative competitive reverse transcription-polymerase chain reaction. RESULTS: Incubation of HUVECs with AngII for 24 h significantly increased LOX-1 protein expression (P<0.001). The increase was dependent on AngII concentration (10(-5)mol/L approximate, equals 10(-9)mol/L). LOX-1mRNA expression was also induced by AngII, and after 24 h incubation of AngII(10(-5)mol/L approximate, equals 10(-8)mol/L), LOX-1mRNA expression increased 4.43, 4.25, 2.71, 1.84 times, respectively. After treatment with 10(-6) mol/L AngII for 3 h, LOX-1 expression (protein and mRNA) was elevated (P<0.001) in HUVECs, reaching its maxium at 24 approximate, equals 36 h. CONCLUSION: AngII upregulates LOX-1 expression concentration-dependently and time-dependently in HUVECs.