Cardiac metallothionein overexpression improves cardiac contractile function and attenuates oxidative stress in lipopolysaccharide-treated mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>This study was designed to examine the impact of the antioxidant metallothionein (MT) on cardiac contractile, intracellular Ca(2+) function and oxidative stress in lipopolysaccharide (LPS)-treated mice.</p><p><b>METHODS</b>Weight and age matched adult male FVB and cardiac-specific MT-overexpressing transgenic mice were injected intraperitoneally with 4 mg/kg Escherichia Coli LPS dissolved in sterile saline or an equivalent volume of pathogen-free saline (control groups). Six hours following LPS or saline injection, cardiac geometry and function were evaluated in anesthetized mice using the 2-D guided M-mode echocardiography. Mechanical and intracellular Ca(2+) properties were examined in hearts. Cell shortening and relengthening were assessed using the following indices: peak shortening (PS)-indicative of the amplitude a cell can shorten during contraction; maximal velocities of cell shortening and relengthening (± dl/dt)-indicative of peak ventricular contractility; time-to-PS (TPS)-indicative of systolic duration; time-to-90% relengthening (TR(90))-indicative of diastolic duration (90% rather 100% relengthening was used to avoid noisy signal at baseline concentration). The 360 nm excitation scan was repeated at the end of the protocol and qualitative changes in intracellular Ca(2+) concentration were inferred from the ratio of fura-2 fluorescence intensity (FFI) at two wavelengths (360/380). Fluorescence decay time was measured as an indicator of the intracellular Ca(2+) clearing rate. Glutathione/glutathione disulfide ratio and ROS generation were detected as the markers of oxidative stress.</p><p><b>RESULTS</b>Heart rate was increased while EF was reduced in LPS-FVB mice and heart rate was reduced and EF increased in MT-LPS transgenic mice [(528 ± 72) beats/min vs (557 ± 69) beats/min, (66 ± 14)% vs (42 ± 10)%, P < 0.05]. Cardiomyocytes from the LPS treated FVB mice displayed significantly reduced peak shortening (PS) and maximal velocity of shortening/relengthening (±dl/dt) associated with prolonged time-to-90% relengthening (TR(90)), these effects were attenuated in cardiomyocytes from the MT-LPS mice [PS(5 ± 1.1)% vs (7.2 ± 0.8)%, dl/dt(160 ± 15) µm/s vs (212 ± 36) µm/s, -dl/dt (175 ± 32) µm/s vs (208 ± 29) µm/s, TR(90) (0.24 ± 0.03)s vs (0.19 ± 0.02)s, P < 0.05]. LPS treated mice showed significantly reduced peak intracellular Ca(2+) and electrically-stimulated rise in intracellular Ca(2+) as well as prolonged intracellular Ca(2+) decay rate without affecting the basal intracellular Ca(2+) levels, again, these effects were significantly attenuated in MT-LPS transgenic mice. Metallothionein overexpression also ablated oxidative stress [reduced ROS generation and increased glutathione/glutathione disulfide ratio, ROS (0.35 ± 0.08) A/µg protein vs (0.24 ± 0.03) A/µg protein]. GSH/GSSG 2.1 ± 0.2 vs 2.6 ± 0.4, P < 0.05.</p><p><b>CONCLUSION</b>MT overexpression improved cardiac function and ablated oxidative stress in LPS treated mice.</p>

Atorvastatin inhibits scavenger receptor A and monocyte chemoattractant protein-1 expressions in foam cell / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of atorvastatin on expressions of scavenger receptor A and secretion of monocyte chemoattractant protein-1 (MCP-1) in foam cells.</p><p><b>METHODS</b>THP-1 cells were induced to differentiate into macrophages by PMA and treated with 0.1% BSA (control), ox-LDL (100 mg/L) or ox-LDL plus atorvastatin (5, 10, 20 micromol/L) for 24 hours. MCP-1 concentration in cell substratum was measured by ELISA. Scavenger receptor A expression was observed under fluorescent microscope after incubated with DiI-Ac-LDL. The relationship between concentration of MCP-1 and the activity of scavenger receptor A was also analyzed.</p><p><b>RESULTS</b>Compared to the control cells, MCP-1 concentration in ox-LDL treated cells was significantly increased after 6 hours, peaked at 12 hours and was still significantly increased after 24 hours (all P < 0.05 vs. baseline). The activity of scavenger receptor A was also significantly increased in ox-LDL treated cells (P < 0.01 vs. control). The activity of scavenger receptor A proteins correlated positively to the concentration of MCP-1 in ox-LDL treated cells (r = 0.683, P < 0.01). Atorvastatin significantly attenuated these changes in a dose-dependent manner.</p><p><b>CONCLUSIONS</b>Scavenger receptor A and MCP-1 expressions were significantly increased in the course of monocyte lines THP-1 differentiating into macrophages and foam cells. The anti-atherosclerosis effect of atorvastatin might be partly achieved by inhibiting the secretion of MCP-1 and expression of scavenger receptor A in foam cells.</p>

Association of angiotensin I converting enzyme 2 gene polymorphism with essential hypertension in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the genetic variants of angiotensin I converting enzyme 2 (ACE2) gene in a Chinese population and to determine whether the ACE2 gene polymorphisms are associated with essential hypertension (EH).</p><p><b>METHODS</b>Seven hundred and forty-five patients with EH and 362 normal blood pressure controls were included in the study to assess the contribution of polymorphism of ACE2 gene. Direct DNA sequencing was performed to detect the single nucleotide polymorphisms (SNPs) in 20 subjects who were randomly selected from the EH patients.</p><p><b>RESULTS</b>One SNP named G8790A located in the 4th base of the third intron was found in the 20 patients. The genotyping data indicate that the A allele frequency in male EH patients complicated with cardiac incompetence(55%) is significantly different from that in the control group(43.3%)(P<0.01). The A allele frequency in female patients with cardiac incompetence (56.1%) is higher than that in the controls (50.5%), but the difference does not reach statistical significance.</p><p><b>CONCLUSION</b>The G8790A polymorphism may be related to the essential hypertension with cardiac incompetence in Chinese population. Additional investigation will be need to confirm the association.</p>

Effect of combined therapy of shenmai and compound danshen injection on myocardial reperfusion injury after percutaneous coronary intervention in patients with acute myocardial infarction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of combined therapy of shenmai and compound danshen injection (SM-DS) on myocardial reperfusion injury after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).</p><p><b>METHODS</b>Thirty-eight AMI patients who received PCI were randomly divided into two groups, the 19 patients in the treated group were treated with SM-DS before and after PCI. Serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in patients' venous blood were measured at different time-points, and the integrated left ventricular ejection isometric index (Tei) was determined by echocardiogram.</p><p><b>RESULTS</b>As compared with before operation in the treated group, MDA was higher and SOD was lower at 2 hrs, 24 hrs after operation (P < 0.05); IL-6 and TNF-alpha were significantly lower at 24 hrs, 48 hrs and 1 week (P < 0.05, P < 0.01) and the Tei began to be improved at 24 hrs (P < 0.05) and significantly improved at 1 week after operation (P < 0.01). While in the control group, MDA was higher and SOD was obviously lower at 2 hrs and 24 hrs (P < 0.01); lowering of IL-6 and TNF-alpha appeared at 1 week (P < 0.05) and improving of Tei index revealed 1 week after operation respectively (P < 0.05). Comparison between the two groups showed significant difference in levels of MDA and SOD at 2 hrs and 24 hrs (P < 0.01); significant difference in levels of IL-6, TNF-alpha at 24 hrs, 48 hrs and 1 week; and in Tei index at 24 hrs and 1 week after operation (P <0.05).</p><p><b>CONCLUSION</b>SM-DS could reduce the myocardial reperfusion injury in patients with AMI after PCI.</p>

Change of peripheral blood monocytes derived macrophage scavenger receptors activity in patients with coronary heart disease, and the intervention effect of ginkgo biloba extract / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the activity of peripheral blood monocytes (PBMs) derived macrophage scavenger receptors (MSR) and changes of serum inflammatory factor in peripheral blood in patients with coronary heart disease (CHD), and to evaluate the effect of Ginkgo biloba extract (GBE) on the MSR activity, to explore the relationship between inflammatory factor and scavenger receptors activity as well as the possible mechanism of GBE in stabilizing the atheromatous plaque.</p><p><b>METHODS</b>Ninety-seven CHD patients with normal blood lipids were classified into the stable angina group, the unstable angina group and the acute myocardial infarction group, and 29 healthy persons were taken as control. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in all subjects were determined. And their PBMs were isolated, cultured in vitro, and transferred into macrophage to observe the effect of GBE on the expression of scavenger receptors.</p><p><b>RESULTS</b>The levels of MSR activity, CRP, sICAM-1 and sVCAM-1 in patients with acute myocardial infarction > unstable angina > stable angina > control.</p><p><b>CONCLUSION</b>GBE could down-regulate the MSR activity in CHD patients, which was positively correlated with levels of CRP, sICAM-1 and sVCAM-1. MSR activity could be taken as a monitoring criteria for active degree of vulnerable atherosclerosis plaque. GBE has the effect of suppressing MSR activity.</p>

Analysis of coronary arteriographic and fluorescence fundus angiographic characteristics in type 2 diabetic patients with coronary heart disease / 中华内分泌代谢杂志

Objective To study the relationship between coronary arteriographic and fluorescence fundus angiographic characteristics in type 2 diabetic patients with coronary heart disease.Methods The study was carried out by the analysis of the data from coronary arteriography and fluorescence fundus angiography in 203 type 2 diabetic patients with coronary heart disease in different groups divided according to age or total cholesterol level. Logisitic regression analysis was applied to explore various risk factors to angiographic characteristics.Results With advancing age,there were more involvement of 3 coronary vessels or the left main branch along with stageⅢretinopathy,but less single vessel diseases in the coronary arteries and less stageⅠretinopathy.The difference in coronary angiographic and fluorescence fundus angiographic characteristics between groups with different total cholesterol levels was not significant.Logistic regression analysis suggested that coronary artery diaease was related to age,sex and blood glucose and triglyceride levels while diabetic retinopathy was related to blood glucose level and age.Conclusion There is great difference in coronary arteriography and fluorescence fundus angiography among different age groups.Aging may aggravate the lesions both in the coronary arteries and fundal vessels in type 2 diabetic patients with coronary heart diseease.