急性心肌梗死患者血清sLOX-1、CK-MB水平及意义

目的探讨急性心肌梗死(AMI)患者血清可溶性凝集素样氧化型低密度脂蛋白受体-1(sLOX-1)和心肌型肌酸激酶同工酶(CK-MB)水平及意义。方法选取AMI患者120例(AMI组),同时选取健康体检者120例作为对照组,检测血清sLOX-1、CK-MB水平。结果AMI组患者血清sLOX-1、CK-MB水平明显高于对照组(P<0.05);AMI组左室舒张末期容积指数(LVEDVI)、左室收缩末期容积指数(LVESVI)和左室射血分数(LVEF)分别为(73.39±2.29)mL/m^2、(38.83±9.28)mL/m^2和(47.88±8.29)%;血清sLOX-1、CK-MB与LVEDVI、LVESVI和LVEF未见明显相关性(P>0.05);AMI组重度狭窄患者血清sLOX-1、CK-MB明显高于轻度和中度狭窄患者(P<0.05);中度狭窄患者血清sLOX-1、CK-MB明显高于轻度狭窄患者(P<0.05);血清sLOX-1、CK-MB与Gensini评分呈正相关(G=0.339和0.252,P<0.05),血清sLOX-1与CK-MB呈正相关(r=0.301,P<0.05)。结论急性心肌梗死患者血清SLOX-1、CK-MB水平升高,与冠状动脉狭窄程度有一定相关性。     

Evaluation of subclinical atherosclerosis in Turkish patients with acne vulgaris receiving systemic isotretinoin

Studies conducted on isotretinoin have shown that it may indirectly lead to atherosclerosis. The objective of this study was to determine the effect of systemic isotretinoin on subclinical atherosclerosis. The present study included 63 patients with acne vulgaris who had used isotretinoin for 6 months. Glucose, insulin, and homeostatic model assessment of insulin resistance levels; body mass index; waist circumference; blood pressure; lipid profile; and lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), high‐sensitivity C‐reactive protein, and oxidized low‐density lipoprotein (Ox‐LDL) levels were compared in the patients at the initiation and discontinuation of the treatment. At the discontinuation of the treatment, LOX‐1 and Ox‐LDL levels showed a significant increase (P < .001 and P = .040, respectively). Differences in waist circumference were positively correlated with an increase in LOX‐1 levels (r = .274; P = .030). Isotretinoin causes an increase in the levels of subclinical atherosclerosis markers. Although the present study sample size was small, we believe that caution should be exercised considering the risk of atherosclerosis during isotretinoin use in men with high waist circumference and cardiovascular risk factors; further studies are warranted in this regard.     

Effect of Moderate Wine Consumption on Oxidative Stress Markers in Coronary Heart Disease Patients

Evidence from research studies reports that wine consumption is associated with lower cardiovascular disease risk, partly through the amelioration of oxidative stress. The aim of the present study was to examine the effect of regular light to moderate wine consumption from coronary heart disease (CHD) patients compared to the effect induced by alcohol intake without the presence of wine microconstituents, on oxidation-induced macromolecular damage as well as on endogenous antioxidant enzyme activity. A randomized, single-blind, controlled, three-arm parallel intervention was carried out, in which 64 CHD patients were allocated to three intervention groups. Group A consumed no alcohol, and Group B (wine) and Group C (ethanol) consumed 27 g of alcohol/day for 8 weeks. Blood and urine samples were collected at baseline and at 4 and 8 weeks. Urine oxidized guanine species levels, protein carbonyls, thiobarbituric acid substances (TBARS) levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were measured. Oxidized guanine species and protein carbonyl levels were significantly increased in the ethanol group during the intervention and were significantly decreased in the wine group. These results support the idea that wine’s bioactive compounds may exert antioxidant actions that counteract the macromolecular oxidative damage induced by alcohol in CHD patients.     

氧化低密度脂蛋白对人单核细胞组织因子和基质金属蛋白酶-9活性的影响以及阿托伐他汀的干预作用

目的:探讨他汀类降脂药阿托伐他汀潜在的降脂外机制。方法:人单核细胞来源的巨噬细胞,加入50mg/L氧化低密度脂蛋白(oxLDL)共培养10d,加或不加入不同浓度的阿托伐他汀(浓度范围0.01~0.5μmol/L);酶谱学分析基质金属蛋白酶-9(MMP-9)的活性;一期凝固法测定组织因子(TF)的促凝活性。结果:阿托伐他汀可抑制单核-巨噬细胞的增殖,呈现一定的剂量依赖关系(P<0.05),加入100μmol/L羟甲戊酸后,这种抑制作用消失;0.1μmol/L的阿托伐他汀可显著抑制单核-巨噬细胞表达MMP-9的活性;阿托伐他汀可呈剂量依赖性抑制TF的促凝活性(P<0.05)。结论:阿托伐他汀不仅可抑制单核-巨噬细胞的增殖,而且可抑制单核巨噬细胞活化下表达的MMP-9的活性以及TF的促凝活性。     

Soluble lectin-like oxidized LDL receptor-1 (sLOX-1) as a valuable diagnostic marker for rupture of thin-cap fibroatheroma: Verification by optical coherence tomography

Background

Relationships between plaque morphology on optical coherence tomography (OCT) and biomarker levels in the patients with acute coronary syndrome (ACS) have not been fully investigated.

Methods

ACS patients (n = 128) were prospectively enrolled and their plasma levels of soluble lectin-like oxidized LDL receptor-1 (sLOX-1), high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity troponin T (hs-TnT) were measured. Another set of 20 patients with stable angina pectoris (SAP) without plaque rupture or erosion served as controls. Among 128 ACS patients, 75 patients underwent OCT procedure to evaluate culprit plaque morphology, and were categorized into two groups; ACS with plaque rupture (ruptured ACS; R-ACS, n = 54) and ACS without plaque rupture (non-ruptured ACS; N-ACS, n = 21).

Results

Levels of sLOX-1 (p < 0.001), hs-CRP (p = 0.048) and hs-TnT (p < 0.001) were significantly higher in R-ACS than SAP. Levels of sLOX-1 were also significantly higher in R-ACS than in N-ACS (p < 0.001); whereas levels of hs-CRP (p = 0.675), as well as those of hs-TnT (p = 0.055), were comparable between R-ACS and N-ACS. Comparison of receiver operating characteristic (ROC) curves among sLOX-1, hs-CRP and hs-TnT to differentiate R-ACS from N-ACS revealed that the area under the curve (AUC) values of sLOX-1, hs-CRP and hs-TnT were 0.782, 0.531 and 0.643, respectively. ROC curves, generated for these biomarkers, to differentiate ACS with thin-cap fibroatheroma (TCFA) from those without demonstrated that the AUC values of sLOX-1, hs-CRP and hs-TnT were 0.718, 0.506 and 0.524, respectively.

Conclusion

sLOX-1, but not hs-CRP or hs-TnT, can differentiate ACS with plaque rupture from those without, and ACS with TCFA from those without.     

SIRT3 regulation of mitochondrial oxidative stress

Mitochondria play a central role in the production of reactive oxygen species as byproducts of metabolism and energy production. In order to protect cellular structures from oxidative stress-induced damage, cells have evolved elegant mechanisms for mitochondrial ROS detoxification. The mitochondrial sirtuin, SIRT3, is emerging as a pivotal regulator of oxidative stress by deacetylation of substrates involved in both ROS production and detoxification. This review will summarize recent findings on the regulation of mitochondrial ROS homeostasis by SIRT3.     

心绞痛患者血清sLOX-1含量与冠状动脉病变危险分数相关性研究

目的检测心绞痛患者血清可溶性血凝素样氧化低密度脂蛋白受体-1(sLOX-1)的浓度,选择性冠脉造影评估冠状动脉病变的危险分数,分析血清sLOX-1水平与危险分数的相关性。方法实验分组:心绞痛组,经冠脉造影证实有明显冠脉狭窄的心绞痛患者43例;对照组,经临床检查及冠脉造影排除冠心病的患者15例。两组患者均采集外周血,测定血清sLOX-1浓度。冠脉病变情况以Califf介绍的危险分数进行评价。结果心绞痛患者尤其是不稳定型心绞痛患者血清中sLOX-1浓度均明显增高(P<0.01),与危险分数呈明显正相关(P<0.01)。结论血清sL-OX-1浓度与冠状动脉病变危险分数密切相关,对评估冠状动脉病变的程度和冠心病患者病情监测可能具有重要的临床价值。     

Effects of troglitazone on in vitro oxidation of LDL and HDL induced by copper ions and endothelial cells

Summary Troglitazone is a new oral antidiabetic agent able to reduce lipid peroxidation. In this study we evaluated its effect on the susceptibility of LDL and HDL to in vitro oxidation induced by copper ions and endothelial cells. In Cu ⁺⁺ -induced LDL modification, different amounts of troglitazone were added to aliquots of the same pool of plasma with subsequent ultracentrifuge separation of LDL and HDL. Differences in LDL and HDL susceptibility to in vitro oxidation with Cu ⁺⁺ were studied by measuring the changes in fluorescence intensity (expressed as lag phase). LDL derived from plasma incubated with different amounts of troglitazone were also incubated with umbilical vein endothelial cells (HUVEC), the modification being monitored by LDL relative electrophoretic mobility and fluorescence. During Cu ⁺⁺ - and HUVEC-induced LDL oxidation, the decay rate of vitamin E, and the potency of troglitazone as a radical scavenger in comparison with vitamin E were also studied. Troglitazone determined a significant, dose-dependent decrease in Cu ⁺⁺ -induced LDL and HDL oxidation. Incubation with HUVEC was also followed by a progressive, significant decrease of LDL relative electrophoretic mobility and fluorescence intensity. During Cu ⁺⁺ - and HUVEC-induced-LDL modification, troglitazone significantly reduced the rate of vitamin E decay. In this study we also demonstrated that under the same oxidative stress, troglitazone was much more potent as a radical scavenger than vitamin E. In conclusion, the results demonstrate that troglitazone can reduce LDL and HDL in vitro oxidation and that, during this process, it can protect vitamin E. In addition to ensuring blood glucose control, the drug may therefore be useful in inhibiting lipoprotein peroxidation. [Diabetologia (1997) 40: 165–172] Received: 26 August 1996, and in revised form: 29 October 1996     

氧化低密度脂蛋白、高敏C反应蛋白与冠状动脉支架置入术后再狭窄的关系

目的:探讨氧化低密度脂蛋白(ox-LDL)、高敏C反应蛋白(hs-CRP)与经皮冠状动脉介入治疗(PCI)术后支架内再狭窄的相关性。方法:45例患者PCI术后6~12个月内接受冠状动脉造影复查,其中18例有再狭窄作为再狭窄组,27例无再狭窄作为对照组。2组术后均接受阿司匹林、波立维、他汀类等药物治疗。取2组患者PCI术前、后冠状动脉造影复查时血浆标本,采用酶联免疫吸附法(ELISA)检测血浆ox-LDL水平,超敏免疫比浊法检测血浆hs-CRP水平,酶法测定血脂水平。结果:①再狭窄组PCI术后ox-LDL、hs-CRP水平较术前均明显升高[(1.32±0.35)∶(0.53±0.17)mg/L、(4.82±1.44)∶(3.50±1.18)mg/L],均P0.01;对照组PCI后ox-LDL、hs-CRP水平较术前明显下降[(0.32±0.13)∶(0.55±0.13)mg/L、(2.28±0.71)∶(3.37±1.25)mg/L],均P0.05。②再狭窄组和对照组PCI术前ox-LDL、hs-CRP水平差异无统计学意义,再狭窄组PCI术后ox-LDL、hs-CRP水平显著高于对照组(均P0.01)。③再狭窄组和对照组术后TC、TG、LDL-C水平均较术前明显下降(P0.05),但2组间PCI术前和术后比较均差异无统计学意义(P0.05)。④再狭窄组和对照组术前、术后ox-LDL和hs-CRP水平均呈正相关。结论:PCI术后再狭窄患者血浆ox-LDL及CRP水平明显升高,二者可作为PCI术后再狭窄的预测指标。     

Tissue factor antisense deoxyoligonucleotide prevents monocrotaline/LPS hepatotoxicity in mice

Tissue factor (TF) is a membranous glycoprotein that functions as a receptor for coagulation factor VII/VIIa and activates the coagulation system when blood vessels or tissues are damaged. TF was upregulated in our monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. We tested the hypothesis that TF‐dependent fibrin deposition and lipid peroxidation in the form of oxidized low‐density‐lipoprotein (ox‐LDL) accumulation contribute to liver inflammation induced by MCT/LPS in mice. In the present study, we blocked TF using antisense oligodeoxynucleotides against mouse TF (TF‐ASO). TF‐ASO (5.6 mg kg^?1) was given i.v. to ND4 male mice 30 min after administration of MCT (200 mg kg^?1) p.o. followed after 3.5 h by LPS i.p. (6 mg kg^?1). Blood alanine aminotransferase (ALT), TF, ox‐LDL, platelets, hematocrit and keratinocyte‐derived chemokine (KC) levels were evaluated in different treatment groups. Fibrin deposition and ox‐LDL accumulation were also analyzed in the liver sections using immunofluorescent staining. The results showed that TF‐ASO significantly restored blood ALT, hematocrit and KC levels, distorted after MCT/LPS co‐treatment, as well as preventing the accumulation of ox‐LDL and the deposition of fibrin in the liver tissues, and thereby inhibited liver injury caused by MCT/LPS. In a separate experiment, TF‐ASO administration significantly prolonged animal survival. The current study demonstrates that TF is associated with MCT/LPS‐induced liver injury. Administration of TF‐ASO successfully prevented this type of liver injury. Copyright © 2012 John Wiley & Sons, Ltd.