冠脉PCI治疗后血浆脂蛋白相关磷脂酶A2与基质金属蛋白酶-9水平的变化及临床意义

目的:探讨冠脉经皮冠状动脉介入(PCI)治疗后血浆脂蛋白相关磷脂酶A2(LP-PLA2)与基质金属蛋白酶-9(MMP-9)水平的变化及其临床意义。方法:选择150例急性冠脉综合征(ACS)患者、128例稳定型心绞痛(SAP)患者及100例健康者分为作为ACS组、SAP组及对照组。比较三组入院时血浆MMP-9、LP-PLA2水平及ACS组经PCI治疗前后血浆MMP-9、LP-PLA2水平的变化。结果:与对照组比较,SAP组与ACS组的血浆MMP-9、LP-PLA2水平均明显增高(P0.05);与SAP组比较,ACS组明显增高(P0.05)。与术前比较,ACS组术后血浆MMP-9、LP-PLA2水平明显降低(P0.05)。MMP-9与LP-PLA2在ACS组血浆中呈显著正相关(r=0.617,P0.05),在SAP组与对照组中无相关性(P0.05)。结论:冠脉病变程度越严重,血浆MMP-9和LP-PLA2水平更高;PCI治疗后冠脉斑块趋于稳定,血浆MMP-9和LP-PLA2水平降低,且二者有相关性,提示MMP-9和LP-PLA2参与冠状动脉粥样硬化的发病与发展,且对预测ACS高危人群及评价疗效有一定的临床价值。     

Vagal stimulation suppresses ischemia-induced myocardial interstitial norepinephrine release

Although electrical vagal stimulation exerts beneficial effects on the ischemic heart such as an antiarrhythmic effect, whether it modulates norepinephrine (NE) and acetylcholine (ACh) releases in the ischemic myocardium remains unknown. To clarify the neural modulation in the ischemic region during vagal stimulation, we examined ischemia-induced NE and ACh releases in anesthetized and vagotomized cats. In a control group (VX, n = 8), occlusion of the left anterior descending coronary artery increased myocardial interstitial NE level from 0.46+/-0.09 to 83.2+/-17.6 nM at 30-45 min of ischemia (mean+/-SE). Vagal stimulation at 5 Hz (VS, n = 8) decreased heart rate by approximately 80 beats/min during the ischemic period and suppressed the NE release to 24.4+/-10.6 nM (P < 0.05 from the VX group). Fixed-rate ventricular pacing (VSP, n=8) abolished this vagally mediated suppression of ischemia-induced NE release. The vagal stimulation augmented ischemia-induced ACh release at 0-15 min of ischemia (VX: 11.1+/-2.1 vs. VS: 20.7+/-3.9 nM, P < 0.05). In the VSP group, the ACh release was not augmented. In conclusion, vagal stimulation suppressed the ischemia-induced NE release and augmented the initial increase in the ACh level. These modulations of NE and ACh levels in the ischemic myocardium may contribute to the beneficial effects of vagal stimulation on the heart during acute myocardial ischemia.     

Exercise training improves conduit vessel function in patients with coronary artery disease.

It is well established that endothelial dysfunction is present in coronary artery disease (CAD), although few studies have determined the effect of training on peripheral conduit vessel function in patients with CAD. A randomized, crossover design determined the effect of 8 wk of predominantly lower limb, combined aerobic and resistance training, in 10 patients with treated CAD. Endothelium-dependent dilation of the brachial artery was determined, by using high-resolution vascular ultrasonography, from flow-mediated vasodilation (FMD) after ischemia. Endothelium-independent vasodilation was measured after administration of glyceryl trinitrate (GTN). Baseline function was compared with that of 10 control subjects. Compared with matched healthy control subjects, FMD and GTN responses were significantly impaired in the untrained CAD patients [3.0 +/- 0.8 (SE) vs. 5.8 +/- 0.8% and 14.5 +/- 1.9 vs. 20.4 +/- 1.5%, respectively; both P < 0.05]. Training significantly improved FMD in the CAD patients (from 3.0 +/- 0.8 to 5.7 +/- 1.1%; P < 0.05) but not responsiveness to GTN (14.5 +/- 1.9 vs. 12.1 +/- 1.4%; P = not significant). Exercise training improves endothelium-dependent conduit vessel dilation in subjects with CAD, and the effect, evident in the brachial artery, appears to be generalized rather than limited to vessels of exercising muscle beds. These results provide evidence for the benefit of exercise training, as an adjunct to routine therapy, in patients with a history of CAD.     

Disruption of vagal efferent axon and nerve terminal function in the postischemic myocardium

Despite the importance of vagal control over the ventricle, little is known regarding vagal efferent conduction and nerve terminal function in the postischemic myocardium. To elucidate postischemic changes in the cardiac vagal efferent neuronal function, we measured myocardial interstitial acetylcholine (ACh) levels by using in vivo cardiac microdialysis and examined the ACh responses to electrical stimulation of the vagi or local administration of ouabain in anesthetized cats. Sixty-minute occlusions of the left anterior descending coronary artery (LAD) followed by 60-min reperfusion abolished electrical stimulation-induced ACh release (20.4 +/- 3.9 vs. 0.9 +/- 0.4 nmol/l; means +/- SE, P < 0.01). In different groups of animals, 60-min LAD occlusion followed by 60-min reperfusion decreased but did not completely abolish ouabain-induced release of ACh (9.2 +/- 1.8 vs. 3.9 +/- 0.7 nmol/l; P < 0.05). These results indicate that function of the vagal efferent axon was completely interrupted, whereas the local ACh release was partially suppressed in the postischemic myocardium. The postischemic disruption of vagal efferent neuronal function might exert deleterious effects on cardiac regulation.     

Lymphocyte DNA damage in patients with acute coronary syndrome and its relationship with severity of acute coronary syndrome

OBJECTIVE: The aim of this study was to investigate the association between lymphocyte DNA damage and acute coronary syndromes (ACS). METHODS: The study population contained 53 patients with ACS, 48 patients with stable angina and 35 voluntary healty subjects. DNA damage was assessed by alkaline comed assay in peripheral lymphocyte and plasma levels of total antioxidant capacity (TAC) were determined using a novel automated measurement method. RESULTS: In ACS patients, DNA damage was significantly higher than in patients with stable angina and control subjects (144+/-52 AU, 116+/-37, 68+/-34 AU; for three p<0.001, respectively). The TAC levels in patients with ACS were lower than the other groups (1.24+/-0.31 mmol Trolox equiv./l, 1.46+/-0.29 mmol Trolox equiv./l, p<0.05, respectively). DNA damage values in patients with acute miyocardial infarction were significantly higher than in patients with unstable angina (159.8+/-53.0 AU versus 131.8+/-48.4 AU; p<0.05, respectively). Lymphocyte DNA damage values in patients with ACS showed positive correlation with d-dimer (r=0.880, p<0.001) troponin I (r=538, p<0.001) and C-reactive protein (r=0.544, p<0.001) and negative correlation with TAC (r=-0.346, p=0.011). In multiple linear regression analysis, TAC (beta=-0.213, p=0.001) and d-dimer (beta=0.697, p<0.001) were independent predictors of DNA damage in patients with ACS. CONCLUSIONS:These findings indicate that lymphocyte DNA damage level increases in patients with ACS. Elevated DNA damage may be related with plaque instability and be useful for the identification of patients with acute coronary syndromes.     

不同病情冠心病患者血清心型脂肪酸结合蛋白与颈动脉内膜中层厚度的关系分析

目的:探讨不同病情冠心病患者血清心型脂肪酸结合蛋白(H-FABP)与颈动脉内膜中层厚度(IMT)的关系。方法:选择内蒙古科技大学包头医学院第一附属医院老年科收治的冠心病患者60例,其中稳定型心绞痛(SAP)和急性冠脉综合征(ACS)各30例,根据冠状动脉病变支数将患者分为单支病变组19例、双支病变组19例和多支病变组22例;根据患者冠状动脉血管狭窄程度分为轻度病变组22例、中度病变组17例和重度病变组21例,选择同期健康体检者30例作为对照组。比较各组颈动脉IMT及血清H-FABP水平,并分析其相关性。结果:ACS组颈动脉IMT及血清H-FABP水平显著高于SAP组和对照组,SAP组颈动脉IMT及血清H-FABP水平显著高于对照组(P<0.05)。不同冠状动脉病变支数、病变程度冠心病患者颈动脉IMT及血清H-FABP水平整体比较差异有统计学意义(P<0.05),多支病变组和双支病变组血清H-FABP水平比较无统计学意义(P>0.05)。Spearman相关分析显示,冠心病患者血清H-FABP水平与颈动脉IMT呈正相关(r=0.754,P<0.05)。结论:冠心病患者血清H-FABP水平与颈动脉IMT异常升高,其水平随冠状动脉病变程度加重而升高,且两者呈正相关。     

血浆及外周血中性粒细胞内髓过氧化物酶水平在冠心病临床诊断中的意义

目的:研究冠心病患者外周循环血中性粒细胞中髓过氧化物酶指数(MPXI)和血浆中髓过氧化物酶(MPO)浓度的改变及两者间相关性,探讨两者在冠心病临床诊断中的意义。方法:随机选取冠心病患者55例,按病情严重程度分为急性冠脉综征(ACS)组35例[包括不稳定心绞痛(UAP)组21例和急性心肌梗死(AMI)组14例]和稳定心绞痛(SAP)组20例,同时随机选取健康体检人员60例为正常对照组;采用ADVIA2120全自动血细胞分析仪检测MPXI,取血浆用ELISA法检测血浆MPO浓度。结果:ACS组MPXI(6.31±4.24)显著高于SAP组(3.38±2.14)和对照组(2.78±2.12),差异有统计学意义(P<0.05);SAP组MPXI高于正常对照组,差异无统计学意义(P>0.05)。ACS组血浆中MPO(1204.07±838.61 pmol/L)显著高于SAP组(755.97±426.23 pmol/L)和对照组(290.45±99.87 pmol/L),差异有统计学意义(P<0.05);SAP组MPO显著高于正常对照组,差异有统计学意义(P<0.05)。SAP组MPXI与MPO无相关性(r=0.424,P>0.05),ACS组MPXI与MPO呈负相关(r=-0.536,P<0.05)。结论:MPXI和MPO在冠心病的诊断中有意义,MPXI与血浆中MPO在ACS组中呈负相关。     

Metabolic syndrome and endothelial fibrinolytic capacity in obese adults

The metabolic syndrome (MetS) often accompanies obesity and contributes to the increased risk of atherothrombotic events with increased body fatness. Indeed, the risks for coronary artery disease and acute vascular events are greater with obesity combined with MetS compared with obesity alone. Endothelial release of tissue-type plasminogen activator (t-PA) is a key defense mechanism against thrombosis and has been shown to be impaired with obesity. The aim of the present study was to determine whether the presence of MetS exacerbates endothelial fibrinolytic dysfunction in obese adults. Net endothelial release of t-PA was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside in 47 sedentary adults: 15 normal weight (age 57 +/- 2 yr; body mass index 22.9 +/- 0.5 kg/m(2)), 14 obese but otherwise healthy (55 +/- 1 yr; 29.4 +/- 0.3 kg/m(2)), and 18 obese with MetS (55 +/- 2 yr; 32.3 +/- 1 kg/m(2)). MetS was established according to National Cholesterol Education Program ATP III criteria. Net release of t-PA antigen to bradykinin was approximately 50% lower (P < 0.01) in the obese (from 2.5 +/- 1.9 to 37.1 +/- 5.3 ng.100 ml tissue(-1).min(-1)) and obese with MetS (from 0.4 +/- 0.8 to 32.5 +/- 3.8 ng.100 ml tissue(-1).min(-1)) compared with normal-weight (from 0.9 +/- 1.0 to 74.3 +/- 8.1 ng.100 ml tissue(-1).min(-1)) subjects. However, there were no significant differences in the capacity of the endothelium to release t-PA in the obese and obese with MetS adults. These results indicate that the presence of the MetS does not worsen the obesity-related endothelial fibrinolytic dysfunction.     

冠状动脉TF/TFPI与急性冠脉综合征关系的研究

目的：研究急性冠脉综合症患者冠状循环局部血液TF/TFPI改变。方法：入选40名冠状动脉造影患者,其中不稳定心绞痛（Unstable pectoris,UP）20例,稳定性心绞痛（Stable pectoris,SP）和正常对照组各10例。所有受试者在冠状动脉造影时,同时经导管抽取主动脉根部、冠状静脉窦和股静脉血样,采用ELISA法测定血浆TF、TFPI水平,计算TF/TFPI比值。结果：三组受检者基本情况均相似,UA组和SA组冠心病危险因素无统计学差异。股静脉血中TF、TFPI浓度及TF/TFPI比值比较：UA组和SA组血TF水平显著高于对照组,UA组血TF水平显著高于SA组。UA组血TFPI水平低于SA组及对照组;SA组血TFPI水平略低于对照组,但未达到统计学意义;UA组血TF/TFPI比值显著高于对照组和SA组,SA组与对照组比较差异无统计学意义。不同部位血TF、TFPI水平及TF/TFPI比值比较：UA组冠状静脉窦血中TF水平较主动脉根部显著升高,CS-AO差值显著高于FV-AO差值;UA组冠状静脉窦血TFPI水平较主动脉根部有升高趋势,但差异无统计学意义,而TF/TFPI比值较主动脉根部升高,差异有统计学意义,CS-AO差值显著高于FV-AO差值。血TF、TFPI水平及TF/TFPI比值在股静脉与主动脉根部之间差异无统计学意义（P〉0.05）。SA组和对照组血TF、TFPI水平及TF/TFPI比值三部位间差异无统计学意义。结论：冠脉循环TF/TFPI比值能较敏感地反映ACS的情况。     

Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease

Coronary endothelial dysfunction is a powerful prognostic marker in patients with coronary artery disease (CAD) that is centrally related to oxidative inhibition of nitric oxide (NO)-dependent vascular cell signaling. Xanthine oxidase (XO), which both binds to and is expressed by endothelial cells, generates superoxide and hydrogen peroxide upon oxidation of purines. Whether inhibition of xanthine oxidase activity results in improved coronary vasomotor function in patients with CAD, however, remains unknown. We assessed coronary and peripheral (brachial artery) endothelial function in 18 patients (pts; 65+/-8 years, 86% male) with angiographically documented CAD, preserved left ventricular function, and non-elevated uric acid levels (233+/-10 microM). Patients received incremental doses of intracoronary acetylcholine (ACh; 10(-7) to 10(-5) microM), and minimal lumen diameter (MLD) and coronary blood flow (CBF) were assessed before and after intravenous administration of oxypurinol (200 mg). Oxypurinol inhibited plasma XO activity 63% (0.051+/- 0.001 vs 0.019+/- 0.005 microU/mg protein; p<0.01). In pts who displayed endothelial dysfunction as evidenced by coronary vasoconstriction in response to ACh (n=13), oxypurinol markedly attenuated ACh-induced vasoconstriction (-23+/- 4 vs -15+/- 4% at ACh 10(-5) microM, p<0.05) and significantly increased CBF (16+/-17 vs 62+/-18% at ACh 10(-5) microM, p<0.05), whereas in patients with preserved coronary endothelial function, oxypurinol had no effect on ACh-dependent changes in MLD (+2.8+/- 4.2 vs 5.2+/- 0.7%, p>0.05) or CBF (135+/-75 vs 154+/-61%, p>0.05). Flow-mediated dilation of the brachial artery, assessed in eight consecutive patients, increased from 5.1+/-1.5 before to 7.6+/-1.5% after oxypurinol administration (p < 0.05). Oxypurinol inhibition of XO improves coronary vascular endothelial dysfunction, a hallmark of patients with CAD. These observations reveal that XO-derived reactive oxygen species significantly contribute to impaired coronary NO bioavailability in CAD and that XO inhibition represents an additional treatment concept for inflammatory vascular diseases that deserves further investigation.     

Effect of pericardial fluid pro-inflammatory cytokines on hemodynamic parameters

We investigated the effects of pro-inflammatory cytokines of pericardial fluid on hemodynamic parameters in patients undergoing coronary artery surgery. Seventy-eight patients were included in the study and they were allocated to three groups: group 1, stable angina pectoris (SAP, n = 15); group 2, unstable angina pectoris (USAP, n = 34); group 3, post-myocardial infarction (PMI, n = 29). Pericardial fluid and arterial blood samples were obtained from all patients and interleukin (IL)-1beta, IL-2 receptor, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) levels were measured. Pericardial IL-1beta concentration (pg/mL) was significantly higher in the USAP group (26.6 +/- 10.9) compared to the SAP (5.0 +/- 0.1) and PMI (5.8 +/- 1.0) groups. IL-2R, IL-6, IL-8 and TNF-alpha concentrations of pericardial fluid were significantly higher than serum in all groups; difference was more prominent in the PMI group compared to the SAP and the USAP groups. Serum IL-1beta concentrations (pg/mL) were significantly higher in the USAP group (21.8 +/- 3.4) compared to the SAP group (5.0 +/- 0.1) and the PMI group (5.4 +/- 1.6). Cardiac index (CI) before opening the pericardial sac was found to be lower in the USAP group (1.6 +/- 0.3 L/min/m2) compared to the SAP (2.2 +/- 0.5 L/min/m2) and the PMI (2.1 +/- 0.5 L/min/m2) groups (p = 0.028 and p = 0.011, respectively). In the USAP group, there was a relationship between reduction of CI and increase of IL-1beta levels in serum and pericardial fluid.     

Comparison of resistance and conduit vessel nitric oxide-mediated vascular function in vivo: effects of exercise training.

Exercise training improves vascular function in subjects with cardiovascular disease and risk factors, but there is mounting evidence these vascular adaptations may be vessel bed specific. We have therefore examined the hypothesis that exercise-induced improvements in conduit vessel function are related to changes in resistance vessel function. Endothelium-dependent and -independent conduit vessel function were assessed by using wall-tracking of high-resolution brachial artery ultrasound images of the response to flow-mediated dilation (FMD) and nitroglycerine [glyceryl trinitrate (GTN)] administration. Resistance vessel endothelium-dependent and -independent function were assessed using intrabrachial administration of acetylcholine (ACh) and nitroprusside (SNP). Randomized crossover studies of 8-wk exercise training were undertaken in untreated hypercholesterolemic (n = 10), treated hypercholesterolemic (n = 10), coronary artery disease (n = 8), and Type 2 diabetic subjects (n = 15). Exercise training significantly enhanced responses to ACh (P < 0.05) and FMD (P < 0.0001). There were no significant changes in either SNP or GTN responses. The correlation between ACh and FMD responses at entry was not significant (r = 0.186; P = 0.231), and training-induced changes in the ACh did not correlate with those in FMD (r = -0.022; P = 0.890). Similarly, no correlation was evident between the SNP and GTN responses at entry (r = -0.010; P = 0.951) or between changes in these variables with training (r = -0.211; P = 0.191). We conclude that, although short-term exercise training improves endothelium-dependent nitric oxide-mediated vascular function in both conduit and resistance vessels, the magnitude of these improvements are unrelated.     

急性冠脉综合征患者PAPP-A基因IVS6+95(C/G)多态性与血浆PAPP-A水平及斑块性质的相关性

为研究湖北十堰地区急性冠脉综合征(ACS)患者PAPP-A基因IVS6 +95(C/G)多态性与血浆PAPP-A水平和斑块性质的相关性,随机选择215例ACS患者(包括58例急性心肌梗死(AMI)患者、73例不稳定型心绞痛(UAP)患者和84例稳定型心绞痛(SAP)患者)及142例健康对照者作为研究对象,检测PAPP-A基因IVS6+ 95 (C/G)多态性和血浆PAPP-A浓度,并进行统计学分析.结果显示,AMI组、UAP组和SAP组的PAPP-A浓度具有极显著差异(p＜0.01),在稳定性斑块和易损性斑块组间的PAPP-A浓度亦具有极显著差异(p＜0.01);AMI组、UAP组和SAP组与对照组间的基因型频率和等位基因频率具有显著差异(p＜0.05);在ACS组和对照组中,组内各类基因型人群的血浆PAPP-A浓度的差异不显著(p＞0.05).结果表明,PAPP-A基因IVS6+ 95多态性与急性冠脉综合征患者密切相关,血浆PAPP-A浓度与斑块性质相关,能够反映ACS患者斑块的易损性,是ACS患者危险分层的标志物.     

Coronary plaque injury triggers neutrophil activation in patients with coronary artery disease

Activation of leukocytes, in particular polymorphonuclear neutrophils (PMN), is considered an early event in unstable coronary disease. Upon activation PMN liberate myeloperoxidase (MPO), an enzyme which binds to the vessel wall and depletes vascular NO bioavailability. Using coronary balloon angioplasty as a trigger to provoke coronary plaque injury, we assessed the time course of neutrophil activation, local and peripheral levels of myeloperoxidase, and systemic vascular NO bioavailability in patients with stable coronary artery disease. Twenty-four patients with stable CAD were enrolled prior to undergoing percutaneous interventions (PCI, n=14) and diagnostic coronary angiography (n=10), respectively. Following angioplasty arterial MPO plasma levels increased (231.5+/-67.6 to 273.8+/-80.4 pg/mg protein; P<0.01) whereas MPO levels in the coronary sinus decreased (240.8+/-74.4 vs 205.4+/-60.1 pg/mg protein; P<0.01) in the absence of elevated serum markers for myocardial necrosis. Following PCI, patients revealed impaired vascular NO bioavailability as reflected by reduced brachial flow-mediated dilation (FMD; 6.25+/-3.03 to 4.90+/-2.70%; P<0.01), whereas FMD increased in the angiography group. Coronary plaque injury provokes rapid activation of PMN in the absence of myocardial necrosis; the coronary circulation emerges as a primary site for deposition of MPO following injury of the coronary vessel wall. Activation of PMN with release of MPO is not only restricted to the target site, but can be assessed systemically and may represent a critical mechanistic link for impaired systemic vascular NO bioavailability in patients suffering unstable coronary disease.     

血清MCP-1、RANTES及CysC联合检测对急性冠状动脉综合征的诊断价值

目的:探讨联合检测血清单核细胞趋化蛋白-1(MCP-1)、活化T细胞趋化因子(RANTES)及半胱氨酸蛋白酶抑制剂C(Cys C)对急性冠状动脉综合征(ACS)患者的早期诊断和预后评估价值。方法:选择200例于2012年10月到2013年10月在本院就诊的冠心病患者200例,其中ACS患者120例(为ACS组),另稳定型心绞痛(SAP)患者80例(SAP组),另选择同期40例健康人为对照组。115例患者有冠状动脉粥样硬化,其中40例钙化斑块组、42例纤维斑块组及33例软斑块组,进行CT检查;用双抗体夹心酶联免疫(ELISA)法检测患者血清MCP-1、RANTES、Cys C及高敏C反应蛋白(Hs-CRP)水平,并用logistic回归方程评价联合检测MCP-1、RANTES及Cys C预测ACS的效果。结果:与SAP组、对照组相比,ACS组患者MCP-1、RANTES、Cys-C、Hs-CRP、LDL-C及空腹血糖(FBG)浓度均明显升高(P0.05);HDL-C浓度明显降低(P0.05);与纤维斑块组、钙化斑块组相比,软斑块组MCP-1、RANTES及Cys-C浓度均明显升高(P0.05);与钙化斑块组相比,纤维斑块组MCP-1、RANTES及Cys-C浓度均明显升高(P0.05);联合检测血清MCP-1、RANTES、Cys-C预测ACS患者,阳性准确率为89.2%,阴性准确率为92.5%,综合准确率为90.8%,明显高于单纯Hs-CRP的检测方法(P0.05)。结论:血清MCP-1、RANTES及Cys C联合检测对急性冠状动脉综合征的诊断效果优于单纯检测Hs-CRP。该联合检测方法具有一定的临床应用价值。     

Mild inflammatory activation of mammary arteries in patients with acute coronary syndromes

Acute coronary syndromes (ACS) are characterized by multiple unstable coronary plaques and elevated circulating levels of inflammatory biomarkers. The endothelium of internal mammary arteries (IMA), which are atherosclerosis resistant, is exposed to proinflammatory stimuli as vessels that develop atherosclerosis. Our study investigated the IMA endothelial expression of inflammatory molecules in patients with ACS or chronic stable angina (CSA). IMA demonstrated normal morphology, intact endothelial lining, and strong immunoreactivity for glucose transporter 1. E-selectin expression was observed more frequently in IMA of ACS patiention than CSA patients (ACS 61% vs. CSA 14%, P = 0.01). High fluorescence for major histocompatibility complex (MHC) was significantly more frequent on the luminal endothelium (ACS 66.7% vs. CSA 17.6%, P = 0.001 for class I; and ACS 66.7% vs. CSA 6.2%, P = 0.0003 for class II-DR) and on the vasa vasorum (ACS 92.9% vs. CSA 33.3% and 7.7%, P = 0.0007 and P < 0.0001 for class I and class II-DR, respectively) of ACS patients than CSA patients. ICAM-1, VCAM-1, Toll-like receptor 4, tissue factor, IL-6, inducible nitric oxide synthase, and TNF-alpha expression were not significantly different in ACS and CSA. Circulating C-reactive protein [ACS 4.8 (2.6-7.3) mg/l vs. CSA 1.8 (0.6-3.5) mg/l, P = 0.01] and IL-6 [ACS 4.0 (2.6-5.5) pg/ml vs. CSA 1.7 (1.4-4.0) pg/ml, P = 0.02] were higher in ACS than CSA, without a correlation with IMA inflammation. The higher E-selectin, MHC class I and MHC class II-DR on the endothelium and vasa vasorum of IMA from ACS patients suggests a mild, endothelial inflammatory activation in ACS, which can be unrelated to the presence of atherosclerotic coronary lesions. These findings indicated IMA as active vessels in coronary syndromes.     

Angiotensin II attenuates myocardial interstitial acetylcholine release in response to vagal stimulation

Although ANG II exerts a variety of effects on the cardiovascular system, its effects on the peripheral parasympathetic neurotransmission have only been evaluated by changes in heart rate (an effect on the sinus node). To elucidate the effect of ANG II on the parasympathetic neurotransmission in the left ventricle, we measured myocardial interstitial ACh release in response to vagal stimulation (1 ms, 10 V, 20 Hz) using cardiac microdialysis in anesthetized cats. In a control group (n = 6), vagal stimulation increased the ACh level from 0.85 +/- 0.03 to 10.7 +/- 1.0 (SE) nM. Intravenous administration of ANG II at 10 microg x kg(-1) x h(-1) suppressed the stimulation-induced ACh release to 7.5 +/- 0.6 nM (P < 0.01). In a group with pretreatment of intravenous ANG II receptor subtype 1 (AT(1) receptor) blocker losartan (10 mg/kg, n = 6), ANG II was unable to inhibit the stimulation-induced ACh release (8.6 +/- 1.5 vs. 8.4 +/- 1.7 nM). In contrast, in a group with local administration of losartan (10 mM, n = 6) through the dialysis probe, ANG II inhibited the stimulation-induced ACh release (8.0 +/- 0.8 vs. 5.8 +/- 1.0 nM, P < 0.05). In conclusion, intravenous ANG II significantly inhibited the parasympathetic neurotransmission through AT(1) receptors. The failure of local losartan administration to nullify the inhibitory effect of ANG II on the stimulation-induced ACh release indicates that the site of this inhibitory action is likely at parasympathetic ganglia rather than at postganglionic vagal nerve terminals.     

Interferon-Gamma Increases the Ratio of Matrix Metalloproteinase-9/Tissue Inhibitor of Metalloproteinase-1 in Peripheral Monocytes from Patients with Coronary Artery Disease

Acute coronary syndromes (ACS) may be triggered by acute infections. Systemic production of interferon gamma (IFN-γ) is induced during infection and regulates the production of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), both important in plaque stability. This study evaluates the effect of IFN-γ on the MMPs/TIMP-1 ratio in cultured monocytes from 30 patients with stable coronary artery disease (CAD), 30 with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI), and 30 healthy blood donors. Supernatant concentrations of MMP-1, -2, -9, and TIMP-1 were measured by enzyme-linked immunoassays. Basal concentration of MMP-1 and TIMP-1 was similar between groups, while MMP-2 was higher in healthy individuals and MMP-9 in patients with UA/NSTEMI. Upon IFN-γ stimulation, MMP-9 secretion increased in all groups, while TIMP-1 decreased only in patients with CAD, which in turn result in a strikingly elevation in their mean MMP-9/TIMP-1 ratio. MMP-1/TIMP-1 and MMP-2/TIMP-1 ratios were <1.0 in basal conditions and after stimulation in all groups. Our results suggest that nonstimulated monocytes from patients with stable CAD show a similar behavior than those from healthy individuals. However, stimulation with IFN-γ induces an increase on the MMP-9/TIMP-1 ratio as high as that found in patients with ACS. Thus, it may bring biological plausibility to the association between acute infections and the development of ACS.     

Elevated plasma levels of human urotensin-II immunoreactivity in congestive heart failure

Human urotensin-II (hU-II) is the most potent endogenous cardiostimulant identified to date. We therefore determined whether hU-II has a possible pathological role by investigating its levels in patients with congestive heart failure (CHF). Blood samples were obtained from the aortic root, femoral artery, femoral vein, and pulmonary artery from CHF patients undergoing cardiac catheterization and the aortic root from patients undergoing investigative angiography for chest pain who were not in heart failure. Immunoreactive hU-II (hU-II-ir) levels were determined with radioimmunoassay. hU-II-ir was elevated in the aortic root of CHF patients (230.9 +/- 68.7 pg/ml, n = 21; P < 0.001) vs. patients with nonfailing hearts (22.7 +/- 6.1 pg/ml, n = 18). This increase was attributed to cardiopulmonary production of hU-II-ir because levels were lower in the pulmonary artery (38.2 +/- 6.1 pg/ml, n = 21; P < 0.001) than in the aortic root. hU-II-ir was elevated in the aortic root of CHF patients with nonischemic cardiomyopathy (142.1 +/- 51.5 pg/ml, n = 10; P < 0.05) vs. patients with nonfailing hearts without coronary artery disease (27.3 +/- 12.4 pg/ml, n = 7) and CHF patients with ischemic cardiomyopathy (311.6 +/- 120.4 pg/ml, n = 11; P < 0.001) vs. patients with nonfailing hearts and coronary artery disease (19.8 +/- 6.6 pg/ml, n = 11). hU-II-ir was significantly higher in the aortic root than in the pulmonary artery and femoral vein, with a nonsignificant trend for higher levels in the aortic root than in the femoral artery. The findings indicated that hU-II-ir is elevated in the aortic root of CHF patients and that hU-II-ir is cleared at least in part from the microcirculation.     

Heterogeneity in conduit artery function in humans: impact of arterial size

To determine whether conduit artery size affects functional responses, we compared the magnitude, time course, and eliciting shear rate stimulus for flow-mediated dilation (FMD) in healthy men (n = 20; 31 +/- 7 yr). Upper limb (brachial and radial) and lower limb (common and superficial femoral) FMD responses were simultaneously assessed, whereas popliteal responses were measured in the same subjects during a separate visit. Glyceryl trinitrate (GTN)-mediated responses were similarly examined. Edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate conduit artery diameter, blood flow, and shear rate continuously across the cardiac cycle. Baseline artery size correlated inversely with the FMD response (r = -0.57, P < 0.001). Within-artery comparisons revealed a significant inverse correlation between artery size and FMD% for the radial (r = -0.66, P = 0.001), brachial (r = -0.55, P = 0.01), and popliteal artery (r = -0.48, P = 0.03), but not for the superficial and common femoral artery. Normalization of FMD responses for differences in eliciting shear rate did not abolish the between-artery relationship for artery function and size (r = -0.48, P < 0.001), suggesting that differences between artery function responses were not entirely due to size-related differences in shear rate. This was reinforced by a significant between-artery correlation for GTN responses and baseline artery size (r = -0.74, P < 0.001). In summary, systematic differences exist in vascular function responses of conduit arteries that differ in size. This raises the possibility that differences in artery size within or between individuals may influence functional responses.