Enhanced levels of platelet P-selectin and circulating cytokines in young patients with mild arterial hypertension

BACKGROUND: Emerging evidence links inflammation to atherosclerosis (AS). Although some studies have addressed the role of inflammation in patients with arterial hypertension (AH), its overall contribution in AH is far from being understood. Therefore, the present pilot study was designed to examine the role of platelet P-selectin and various inflammatory mediators in young patients with moderate AH without signs of target organ damage. METHODS AND RESULTS: Fifteen patients with mild AH [33.8 +/- 7.3 years, mean arterial pressure (MAP) 106.6 +/- 10.4 mmHg] and 15 healthy normotensive controls (31.7 +/- 10.6 years) were examined. Platelet P-selectin was analysed by flow cytometry. Plasma levels of monocyte-chemoattractant-protein-1 (MCP-1), high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumour necrosis factor alpha (TNFalpha), and IL-10 levels were measured by enzyme immunoassay (EIA). Patients with mild AH showed significantly enhanced expression of platelet P-selectin [17.2 +/- 5.4 versus 10.6 +/- 4.2 mean fluorescence intensity (MFI), P < 0.001]. P-selectin expression positively correlated with MAP (r = 0.43, P < 0.05). Furthermore, patients with mild AH had significantly enhanced plasma levels of hsCRP (2.7 +/- 3.8 versus 0.6 +/- 0.9 mg/l, P < 0.01), IL-6 (1.4 +/- 0.7 versus 0.6 +/- 0.3 pg/ml, P < 0.001), TNFalpha (2.8 +/- 0.7 versus 2.4 +/- 0.4 pg/ml, P < 0.05), and MCP-1 (291.3 +/- 100.7 versus 214.3 +/- 8.3 pg/ml, P < 0.05). IL-6 levels positively correlated with hsCRP levels (r = 0.47, P < 0.05) and mean arterial pressure (MAP) (r = 0.44, P < 0.05). CONCLUSIONS: This pilot study demonstrates that in an early stage of AH, inflammatory pathways are already activated. Besides pro-inflammatory cytokines, platelets seem to play a significant role in mediating inflammation in AH, which could lead to target organ injury. Further investigations have to clarify the role of early anti-inflammatory therapy, in patients with mild to moderate AH, in alleviating hypertensive target organ damage.     

Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study

OBJECTIVES: This study was performed to assess whether the anti-inflammatory and antiatherogenic effects of pioglitazone suggested by animal experiments are reproducible in man and independent from improvements in metabolic control. BACKGROUND: Type 2 diabetes is associated with increased cardiovascular risk. METHODS: A total of 192 patients were enrolled into a six-month, prospective, open-label, controlled clinical study. They were randomized to receive either pioglitazone (45 mg) or glimepiride (1 to 6 mg, with the intent to optimize therapy). Biochemical and clinical markers to assess therapeutic effects included HbA1c, fasting glucose, insulin, adiponectin, lipids, high-sensitivity C-reactive protein (hsCRP), intracellular adhesion molecule, vascular cell adhesion molecule, vascular endothelial growth factor, fibrinogen, von Willebrand factor, matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, soluble CD40 ligand, and carotid intima-media thickness (IMT). RESULTS: The study was completed by 173 patients (66 female, 107 male; age [+/- SD]: 63 +/- 8 years; disease duration: 7.2 +/- 7.2 years; HbA1c: 7.5 +/- 0.9%; pioglitazone arm: 89 patients). A comparable reduction in HbA1c was seen in both groups (p < 0.001). In the pioglitazone group, reductions were observed for glucose (p < 0.001 vs. glimepiride group at end point), insulin (p < 0.001), low-density lipoprotein/high-density lipoprotein ratio (p < 0.001), hsCRP (p < 0.05), MMP-9 (p < 0.05), MCP-1 (p < 0.05), and carotid IMT (p < 0.001), and an increase was seen in high-density lipoprotein (p < 0.001) and adiponectin (p < 0.001). Spearman ranks analysis revealed only one correlation between the reduction in cardiovascular risk parameters and the improvement in the metabolic parameters (MMP-9 and fasting blood glucose, p < 0.05) CONCLUSIONS: This prospective study gives evidence of an anti-inflammatory and antiatherogenic effect of pioglitazone versus glimepiride. This effect is independent from blood glucose control and may be attributed to peroxisome proliferator-activated receptor gamma activation.     

Anti-inflammatory effects of atorvastatin: modulation by the T-786C polymorphism in the endothelial nitric oxide synthase gene

Statins produce cholesterol-independent, anti-inflammatory effects, which result at least in part from increased endothelial nitric oxide production. These effects may be modulated by polymorphisms in the endothelial nitric oxide synthase (eNOS) gene. Here, we examined whether the T-786C polymorphism of eNOS gene affects the concentrations of markers of atherosclerosis and inflammation (sCD40L, sVCAM-1, sICAM-1, sP-selectin, MCP-1, high sensitivity (hs)-CRP, MMP-2, MMP-9, and TIMP-1). We also studied whether atorvastatin-induced anti-inflammatory effects are modulated by this polymorphism. Healthy male volunteers (N=200), Caucasians, non-smokers, were genotyped for the T-786C polymorphism by restriction fragment length polymorphism. Subjects with TT or CC genotype received placebo for 14 days followed by 14 days of treatment with atorvastatin, 10mg/day p.o. The concentrations of inflammatory markers were measured with ELISA kits or by gelatin zymography. Serum cholesterol and LDL-cholesterol were significantly reduced after atorvastatin treatment in both genotype groups (P<0.05). No significant differences between genotype groups were found in the concentrations of the inflammatory markers after placebo. However, atorvastatin significantly reduced the concentrations of sCD40L, sVCAM-1, sP-selectin and MMP-9 in subjects with CC (but not TT) genotype (P<0.05). While atorvastatin decreased hs-CRP levels in both genotype groups (P<0.05), no significant effects were found on the concentrations of sICAM-1, MCP-1, pro-MMP-9, pro-MMP-2 and TIMP-1. These results suggest no effects for the T-786C polymorphism on the concentrations of inflammatory markers. However, this polymorphism modulates the anti-inflammatory effects of atorvastatin. These findings may be relevant for the primary prevention of cardiovascular events in subjects with CC genotype, who may be at increased cardiovascular risk and could benefit from treatment with statins.     

LDL-apheresis reduces P-Selectin, CRP and fibrinogen -- possible important implications for improving atherosclerosis

Although it is known that LDL-apheresis improves coronary artery stenosis (CAS) as well as ischemic limbs seen in patients with peripheral arterial occlusive disease (PAOD), the underlying mechanisms remain still unknown. LDL-apheresis might exert its favorable action through anti-inflammatory effects. We studied whether or not serum or plasma levels of P-selectin, high sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1) or fibrinogen could be reduced in patients with PAOD before and after 10 sessions of LDL-apheresis. Sixteen patients (12 patients with hemodialysis, HD) with PAOD were enrolled in the present study. LDL-apheresis was carried out 10 times (treated plasma of 3000 mL) over 5 weeks. Serum levels of P-selectin were significantly reduced from 516 +/- 153 to 290 +/- 52 ng/mL before and after 10-sessions of LDL-apheresis, respectively (P < 0.05). Likewise, serum levels of hsCRP decreased from 9.118 +/- 2.649 to 5.587 +/- 2.445 mg/L (P < 0.01); and plasma fibrinogen levels statistically decreased from 196 +/- 9.82 to 149 +/- 7.97 mg/dL (P < 0.01), whereas serum levels of MCP-1 were not significantly changed. The favorable actions of LDL-apheresis might include anti-inflammatory effects, which could lead to an improvement of CAS and PAOD. Moreover, this intervention might be applicable for patients with atherosclerotic cardiovascular disorders, particularly in patients with HD.     

Atorvastatin treatment decreases inflammatory and proteolytic activity in patients with hypercholesterolemia

BACKGROUND: Statins have anti-inflammatory and anti-platelet effects, which are known as non-lipid effects. Statin treatment can decrease endogenous inflammatory response. AIM: To study the effects of atorvastatin on matrix metalloproteinase-9 (MMP-9) and high sensitive C-reactive protein (hs-CRP) - markers of the proteinolytic and inflammatory activity. METHODS: In this prospective study 44 patients with hypercholesterolemia were randomly assigned into 2 groups; Group 1 (n=22) treated with atorvastatin and diet for 2 months, and Group 2 (n=22) - diet alone. MMP-9 and hs-CRP were measured at baseline and two months later. RESULTS: Groups were matched for age, sex and baseline characteristics. Lipid levels decreased by 32% (LDL from 153.9+/-26.6 to 94.5+/-20.8 mg/dl, p<0.005) in the atorvastatin group and by 9% in the diet alone group. Atorvastatin lowered plasma CRP from 5.16+/-1.9 to 2.88+/-1.06 mg/L (p<0.001) and MMP-9 activity from 64.3+/-28.1 to 35.4+/-20.0 ng/ml (p<0.0001). Atorvastatin-induced reductions in CRP and MMP-9 were greater than in the diet alone group. MMP-9 levels did not show significant changes in Group 2 after two months of diet. CONCLUSIONS: Atorvastatin treatment decreases inflammatory and proteolytic activity in patients with hypercholesterolemia.     

Racial difference in endothelial function: role of the infective burden

There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27+/-8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28+/-9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9+/-3.5% versus 11.6+/-3.0%, p<0.01) and increased values of hsCRP (0.35+/-0.15 mg/dL versus 0.07+/-0.08 mg/dL, p<0.05), white cells (8578+/-1041/mmc versus 5833+/-998/mmc, p<0.01) and adhesion molecules (respectively: sVCAM-1 945+/-142 versus 779+/-93, sICAM-1 534+/-107 ng/mL versus 325+/-80 ng/mL; both p<0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5+/-1 versus 2+/-1, p<0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r=-0.49; sICAM-1 r=-0.50, both p<0.05), hsCRP (r=-0.47, p<0.05) and white blood cells (r=-0.43, p<0.05). TIB was associated with brachial FMV (r=-0.64, p<0.05), sVCAM-1 (r=0.55, p<0.05) and hsCRP (r=0.47, p<0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: beta=-0.49, -0.19, -0.54, all p<0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.     

Anti-inflammatory effects of pioglitazone and/or simvastatin in high cardiovascular risk patients with elevated high sensitivity C-reactive protein: the PIOSTAT Study.

OBJECTIVES: The purpose of this study was to test the safety and efficacy of pioglitazone and simvastatin in combination versus each drug individually in non-diabetic subjects with cardiovascular disease (CVD) and elevated high-sensitivity C-reactive protein (hs-CRP) levels. BACKGROUND: Low-grade inflammation is a pathogenic factor for atherosclerosis. High-sensitivity CRP, matrix metalloproteinase (MMP)-9, and plasminogen activator inhibitor (PAI)-1 are markers of inflammation. Statins and peroxisome proliferator-activated receptor (PPAR)-gamma agonists lower inflammatory markers and reduce CVD in type 2 diabetes. METHODS: In a 12-week, prospective, double-blind trial, 125 subjects were randomized to simvastatin or pioglitazone plus placebo or a simvastatin/pioglitazone combination. We tested changes in hs-CRP by analysis of covariance. A subgroup analysis was performed in patients with and without the metabolic syndrome (MetS). The correlation between changes in hs-CRP and homeostasis model assessment (HOMA; a measure of insulin resistance) was calculated with the Spearman's rank test. RESULTS: At baseline, there were no significant between-group differences. At 12 weeks, pioglitazone and simvastatin monotherapies significantly reduced hs-CRP (3.64 +/- 2.42 mg/l to 2.48 +/- 1.77 mg/l and 3.26 +/- 2.02 mg/l to 2.81 +/- 2.11 mg/l) and the combination regimen had an additive effect (from 3.49 +/- 1.97 mg/l to 2.06 +/- 1.42 mg/l, p < 0.001). For subgroups, the difference between monotherapy and combination therapy was only significant for simvastatin versus simvastatin plus pioglitazone in patients without MetS. Homeostasis model assessment decreased in those receiving pioglitazone, and the correlation between changes in HOMA and hs-CRP was significant (r = 0.43; p < 0.05). The PAI-1 decreased significantly in the pioglitazone groups only, and MMP-9 was also significantly lowered in the pioglitazone groups. No treatment-related serious adverse events occurred in any group. CONCLUSIONS: Pioglitazone, probably by reducing insulin resistance, has additive anti-inflammatory effects to simvastatin in non-diabetic subjects with CVD and high hs-CRP.     

Curcumin's Effect on Inflammatory Response following Percutaneous Coronary Intervention in Adult Patients with Stable Coronary Heart Disease

Cardiovascular diseases play major roles in the health problems worldwide especially in Indonesia. Percutaneous coronary intervention (PCI) is a minimally invasive procedure with relatively low complications. However, high inflammatory response post-PCI has showed adverse events even after administration of standard medication. Previous studies showed that curcumin was able to reduce inflammatory response in adult patients with stable coronary heart disease (CHD). This article determines the efficacy of oral administration of curcumin in reducing inflammatory response post-PCI with stable CHD. A double-blind randomized controlled trial on 50 adult patients comparing curcumin and placebo was performed in Cipto Mangunkusumo General Hospital and Jakarta Heart Center within April and June 2015. Either curcumin (45 mg/day) or placebo was given 7 days prior to PCI until 2 days after PCI. Inflammatory markers (high-sensitivity C-reactive protein [hsCRP] and soluble CD40 ligand [sCD40L]) were measured in three phases (7 days prior PCI, 24 hours post-PCI, and 48 hours post-PCI). There were no significant differences in the reduction of hsCRP and sCD40L between curcumin and placebo groups in three phases of measurement. Curcumin significantly reduce the serum hsCRP ( p  = 0.006) and sCD40L ( p  = 0.002) 7 days before PCI to 48 hours post-PCI. The decrement of hsCRP (−14.2% vs. –7.4%) and sCD40L (−24.3% vs. –13.2%) from 24 to 48 hours post-PCI was higher in the curcumin group than placebo group. The administration of curcumin 45 mg dose daily for 7 days prior PCI until 48 hours post-PCI is useful in reducing inflammatory response post-PCI with stable CHD.     

2型糖尿病患者应用吡格列酮治疗前后血清C反应蛋白的改变

目的观察盐酸吡格列酮治疗2型糖尿病(T2DM)前后血清高敏C反应蛋白(hsCRP)的变化及其影响因素,探讨糖脂代谢与炎症因子的关系。方法采用随机、双盲、安慰剂平行对照方法将130例已合用磺脲类和双胍类药物的T2DM患者随机分至盐酸吡格列酮组及安慰剂组,进行为期12周的临床观察。结果基线hsCRP水平与糖化血红蛋白(HbA1c)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC)、甘油三酯(TG)水平、体质指数、性别均相关。吡格列酮治疗后患者hsCRP水平明显下降(P=0.0030)。而安慰剂组无改变。餐后血糖变化(P<0.01)及空腹血糖水平的变化(P<0.01)与hsCRP变化最相关,其次为LDLC(P<0.01)、HbA1c(P=0.033)及HDLC(P=0.047)的改变。结论T2DM患者慢性高血糖状态与炎症关系密切。吡格列酮治疗在改善糖脂代谢的同时,还具有明显的抗炎作用,使hsCRP水平明显下降。     

Initiation of insulin therapy reduces serum concentrations of high-sensitivity C-reactive protein in patients with type 2 diabetes

Atherosclerosis has highly important chronic inflammatory aspects. We investigated anti-inflammatory effects upon initiating insulin therapy by measuring serum high-sensitivity C-reactive protein (hsCRP) and plasma fibrinogen and serum monocyte chemoattractant protein (MCP)-1in patients with poorly controlled type 2 diabetes. In 18 inpatients with type 2 diabetes, we measured serum hsCRP, plasma fibrinogen, serum MCP-1, body weight (BW), girth, and fasting plasma glucose (FPG) before and 2 weeks (14.0 +/- 2.5 days) after initiation of insulin therapy. Daily insulin doses (in units) were approximately 0.2 x BW (in kilograms). Various changes (ratio) were calculated as the ratio of the value during treatment to the pretreatment value. Significant decreases occurred for log(10) hsCRP and FPG (-0.025 +/- 0.557 mg/L, 215 +/- 64.3 mg/dL v -0.213 +/- 0.571 mg/L, 129.8 +/- 32.1 mg/dL; P =.0121, and P =.00002, respectively). This was particularly true for log(10) hsCRP in patients whose BW was unchanged or increased between measurement (P =.0050). There were no significant differences between pretreatment and treatment values for fibrinogen and MCP-1. However, MCP-1 decreased significantly in the group with high-value in the first time point (MCP-1 > 250 pg/mL, n = 9; P =.0224) compared with the low-value group (MCP-1 < 250 pg/mL, n = 9; P =.3164). No significant correlation was found between hsCRP ratio and fibrinogen ratio, MCP-1 ratio, BW ratio, waist girth ratio, or FPG ratio. In conclusion, newly initiated insulin therapy in patients with poorly controlled type 2 diabetes decreased serum hsCRP. The decrease in hsCRP may have resulted largely from anti-inflammatory effects of insulin.     

Coronary artery disease progression is associated with C-reactive protein and conventional risk factors but not soluble CD40 ligand

BACKGROUND: Coronary artery disease (CAD) is a major cause of death worldwide. Epidemiological studies have documented conventional risk factors; however, no studies to date have addressed the roles of soluble CD40 ligand (sCD40L) and monocyte chemoattractant protein-1 (MCP-1), and there have been few reports on other novel risk factors in CAD progression. The aim of the present study was to explore the roles of novel and conventional risk factors in CAD progression. METHODS: Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of their first catheterization between March 1999 and January 2004 were enrolled. Those who had progression of coronary atherosclerosis were classified into the progression group (n = 66). Those who did not have CAD progression were classified into the nonprogression group (n = 124). RESULTS: There were more cases of diabetes mellitus (36% versus 20%; P = 0.024) and more men (92% versus 81%; P = 0.040) in the CAD progression group than in the nonprogression group, respectively. The progression group also had poorer lipid profiles than the nonprogression group, including higher total cholesterol (188+/-42 mg/dL versus 173+/-39 mg/dL, respectively; P = 0.014) and low density lipoprotein cholesterol (122+/-38 mg/dL versus 112+/-36 mg/dL, respectively; P = 0.025). In terms of inflammatory markers, progression patients had higher baseline high-sensitivity C-reactive protein (hs-CRP) concentrations (P = 0.018), which was also related to the subsequent angiographic severity score changes; however, sCD40L (6182+/-4352 pg/mL versus 6244+/-4602 pg/mL; P = 0.961), MCP-1 (427+/-540 pg/mL versus 341+/-128 pg/mL; P = 0.580) and adhesion molecules concentrations were indifferent between the progression group and the nonprogression group, respectively. Using a multivariate logistical regression model, the ORs for predicting progression were 2.19 for diabetes mellitus, 2.04 for hypercholesterolemia and 1.52 for hs-CRP (P < 0.05). CONCLUSION: In the present study, only conventional risk factors, and particularly hs-CRP, were markers for predicting CAD progression. Novel risk factors, such as concentrations of sCD40L, MCP-1 and adhesion molecules, did not play significant roles.     

吡格列酮对糖尿病大鼠血清MMP-9水平及其外周血单核细胞中MMP-9表达的影响

目的:观察过氧化物酶体增殖物激活受体γ(PPARγ)配体吡格列酮对糖尿病大鼠血清基质金属蛋白酶9(MMP-9)浓度和外周血单核细胞中MMP-9表达的影响。方法:40只Wistar大鼠随机分为5组,即对照组、糖尿病组和不同剂量5、10、20mg/(kg.d)吡格列酮治疗组,每组8只。给糖尿病组和3个吡格列酮治疗组大鼠腹腔注射链脲霉素制作糖尿病大鼠模型后,各吡格列酮治疗组以不同剂量的吡格列酮灌胃:5、10、20mg/(kg.d),共28d;对照组和糖尿病组以等量生理盐水灌胃。比较治疗前、后的血清MMP-9浓度的变化。分离大鼠外周血单核细胞,用RT-PCR和Westernblot检测MMP-9表达的变化。结果:与对照组比较,吡格列酮降低血清MMP-9的浓度(P0.05),降低外周血单核细胞中MMP-9的表达。结论:吡格列酮可以降低糖尿病大鼠血清MMP-9浓度及外周血单核细胞中MMP-9的表达,提示其在降糖之外还具有心血管保护作用。     

Effect of transdermal hormone replacement therapy on carotid artery wall thickness and levels of vascular inflammatory markers in postmenopausal women.

Carotid intima-media thickness (IMT) and vascular inflammatory markers have been shown to be involved in atherosclerosis. This study was designed to investigate the effect of transdermal hormone replacement therapy (HRT) on carotid IMT and vascular inflammatory markers in postmenopausal women and to explore the interrelationship between the change in carotid IMT and the changes in vascular inflammatory markers. Thirty-five postmenopausal women (mean age 57.0+/-7.7 years) received transdermal HRT (continuous 17beta-estradiol patch [36 microg/day] plus cyclic oral medroxyprogesterone acetate [2.5 mg/day, for 12 days/ month]) for 12 months, and 32 controls (mean age 58.0+/-7.5 years) did not. Carotid IMT, assessed by ultrasound, and circulating vascular inflammatory markers, i.e., C-reactive protein (CRP), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, E-selectin, monocyte chemoattractant protein (MCP)-1, and matrix metalloproteinase (MMP)-9 were measured before and after 12 months of treatment. In the HRT group, carotid IMT decreased significantly (p<0.01), from 0.71+/-0.13 mm to 0.65+/-0.12 mm, and the ICAM-1, VCAM-1, E-selectin, and MCP-1 levels decreased significantly (p<0.01 for all), but the CRP and MMP-9 levels remained unchanged. Carotid IMT and vascular inflammatory markers were unchanged in the control group. In the HRT group, the change in carotid IMT was significantly correlated with the change in serum E-selectin (r=0.38, p<0.05), but not with the changes in other vascular inflammatory markers. These results suggest that transdermal HRT reduced carotid artery wall thickness, and that the reduction may have been induced by an antiatherosclerotic effect combined with the direct effect of estrogen and decreased levels of estrogen-induced E-selectin.     

急性心肌梗死早期普伐他汀治疗对血浆CD40L、金属蛋白酶-9及C反应蛋白的影响

目的　观察较大剂量普伐他汀治疗急性心肌梗死患者 3d后金属蛋白酶 9(MMP 9)、可溶性白细胞分化抗原 40配体 (sCD40L)及C 反应蛋白 (CRP)的变化 ,以了解短期普伐他汀治疗对斑块稳定和免疫炎症抑制的影响。方法　 35例急性心肌梗死患者随机分为常规治疗组 (无服用任何调脂药物 ,17例 )和普伐他汀组 ( 40mg/d ,18例 )治疗 ,测定治疗前后sCD40L、MMP 9、CRP和血脂水平的变化。结果　二组治疗前后血脂各组成分的变化差异均无显著性 ,而普伐他汀治疗组治疗后sCD40L、MMP 9及CRP水平分别降低 38%、48%、33%,与治疗前比较有统计学差异 (P <0 0 5 )。在普伐他汀治疗组 ,sCD40L、MMP 9的降低与TC(r =0 0 9,P =0 5 7;r =0 15 ,P =0 38)、LDL C(r =0 0 8,P =0 87;r= 0 0 3 ,P =0 83)的下降百分数之间无相关关系。结论　在急性心肌梗死的早期予以 3d的普伐他汀治疗 ,可明显减低血浆炎症因子的水平、可能有利于动脉粥样硬化斑块的稳定。     

Lower plasma adiponectin concentration predicts the efficacy of pioglitazone in diabetic patients

AIM: To investigate clinical efficacy of pioglitazone in association with plasma adiponectin concentration in type 2 diabetic patients. METHODS: Ten diabetic patients were treated with 15 or 30 mg of pioglitazone for 8 weeks, and association between plasma adiponectin concentration before treatment and decrease in glycated albumin levels was examined. RESULTS: Treatment with pioglitazone for 8 weeks lowered glycated albumin level (27.1 +/- 1.2 to 23.8 +/- 1.4%, p < 0.05), and inverse relationship between changes in glycated albumin and plasma adiponectin concentration before treatment was revealed (r = -0.66, p < 0.05). Plasma adiponectin concentrations of patients whose glycated albumin level reduced by more than 10% of the levels before treatment were significantly lower than those of patients whose glycaemic control was affected less (5.2 +/- 0.6 vs. 8.0 +/- 1.0 micro g/ml, p < 0.05). CONCLUSION: Lower plasma adiponectin concentration predicts the clinical efficacy of pioglitazone.     

老年人冠状动脉介入治疗术后氯吡格雷抵抗与炎性因子的关系

目的 观察冠状动脉支架植入后发牛氯吡格霄抵抗的老年冠心病患者术前、术后血清炎症因子的变化,并探讨其临床意义. 方法 选择因冠心病不稳定心绞痛住院并成功接受冠状动脉支架植入术的老年患者93例,分别于术前和术后24 h、7 d、1个月抽取外周血,比浊法检测二磷酸腺苷诱导的血小板聚集率,氯吡格雷抵抗33例(抵抗组)和正常反应60例(非抵抗组).酶联免疫法测定C反应蛋白质(CRP)、可溶性CD40配体(sCD40L)和P-选择素(P-selectin),分析氯吡格雷抵抗与炎症因子的关系. 结果 冠状动脉介入术后24 h、7 d、30 d时氯吡格雷抵抗的发生率为35.5%(33例)、26.9%(25例)、20.4%(19例),抵抗组患者术后24 h、7 d时血CRP水平[(8.8±2.5)mg/L、(5.3±2.5)mg/L]与术前(2.1±1.0)mg/L和非抵抗组[(8.1±2.3)mg/L和(2.5±1.4)mg/L]比较,差异有统计学意义(均P<0.05),30 d时有增高趋势,但差异无统计学意义,术后不同时间点P-selectin水平均较非抵抗组增高(P<0.05).术后24 hsCD40L水平较术前升高(P<0.05).相关分析结果显示,P-selectin水平、吸烟与术后30 d时氯吡格雷抵抗呈正相关(r=1.334,r=1.053,均P<0.05). 结论 冠状动脉支架术后对氯吡格雷具有不同反应性的老年患者血CRP、sCD40L、P-selectin表达存在差异,可能与氯吡格雷抵抗有关,P-selectin水平和吸烟是老年人冠状动脉支架植入术后30 d时氯吡格雷抵抗发生的预测因素.     

Soluble CD40 ligand and atrial fibrillation: relationship to platelet activation, and endothelial damage/dysfunction

Increased plasma soluble CD40L (sCD40L) is present in many cardiovascular diseases and predicts poor outcome, but levels in atrial fibrillation (AF) are unknown. Although the platelet is frequently cited as the source of sCD40L, this view is not universal. We hypothesised (a) raised sCD40L in non-rheumatic AF, and (b) that sCD40L correlates with platelet, but not endothelial, markers, thus suggesting a platelet origin. Plasma sCD40L, platelet marker soluble P-selectin and endothelial markers von Willebrand factor (vWf) and soluble E-selectin were measured by ELISA in 54 AF patients free of diabetes or major cardiovascular disease, and in 28 age/sex matched controls. Median (inter-quartile range) sCD40L in AF was 0.82 (0-4.8) ng/mL compared to 0.21 (0-5.5 ng/mL) in controls (p=0.0397). vWf and soluble P-selectin (p<0.005), but not soluble E-selectin, were raised in AF, but none of the indices inter-correlated significantly. We find that sCD40L is marginally raised in AF but the stimulus for this is unclear. The lack of clear correlation with relevant plasma markers suggests that the source is unlikely to be the endothelium or platelet alone.     

The role of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke

BACKGROUND: Increasing evidences show that disruption of carotid plaque followed by arterio-arterial thromboembolism is an important mechanism in the generation of ischemic stroke. Inflammatory mechanisms play a key role in transforming structurally vulnerable plaques into functionally unstable ones. The purpose of the present study is to evaluate the roles of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke. METHODS: Fifty-two patients with acute ischemic stroke affecting the anterior circulation (stroke group) and 44 with asymptomatic carotid stenosis (asymptomatic group) were investigated. Duplex ultrasonography was used to evaluate the characteristics of carotid plaque and grading the degree of carotid stenosis. Plaque echogenicity was assessed as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. Plaque surface was classified as smooth, irregular, or ulcerated. All subjects had duplex-determined 50% to 99% carotid stenosis. Serum levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinases (TIMP-1), soluble CD40 ligand (sCD40L) and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS: Plaques in the stroke group were echolucent or predominantly echolucent, whereas those of the asymptomatic group were predominantly echogenic or echogenic plaques (P<0.05). Irregular and ulcerated plaques were frequently found in stroke patients, while smooth plaques were frequently detected in asymptomatic patients (P<0.05). Serum levels of MMP-9, sCD40L, hsCRP were higher in stroke than in asymptomatic patients. By contrast, serum TIMP-1 levels were significantly higher in the asymptomatic than in the stroke group. CONCLUSIONS: The results suggest that inflammation plays a crucial role in carotid plaque vulnerability and, together with carotid plaque morphology, in the pathogenesis of acute ischemic stroke.     

Effect of continuous positive airway pressure on soluble CD40 ligand in patients with obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis. CD40-CD40 ligand interaction promotes several proinflammatory mediators and plays a pivotal role in the various stages of atherosclerotic diseases. The present study examines whether CD40 ligation contributes to outcomes in patients with OSAS. METHODS: The study population comprised OSAS patients with an apnea hypopnea index (AHI) > or = 30 (n = 35) and control subjects (AHI < 5; n = 16). We measured serum levels of soluble CD40 ligand (sCD40L), tumor necrosis factor (TNF)-alpha, and hypersensitive C-reactive protein (hsCRP) before and after nasal continuous positive airway pressure (nCPAP) therapy for 3 months. RESULTS: Baseline levels of sCD40L were significantly higher in patients with OSAS (6.93 +/- 4.64 ng/mL) [mean +/- SD] than in control subjects (3.43 +/- 2.11 ng/mL, p < 0.01). Baseline levels of sCD40L positively correlated with TNF-alpha but not with hsCRP. The elevation of sCD40L was improved for 1 night after nCPAP therapy (3.83 +/- 2.78 ng/mL, p < 0.001). Even though patients with severe OSAS did not receive any other medication to control atherosclerotic risk factors for 3 months, nCPAP was continued to reduce the levels of sCD40L. CONCLUSION: The present study suggested that sCD40L is a key factor that links OSAS and atherosclerotic progression.     

Inflammation and postinfarct remodeling: overexpression of IkappaB prevents ventricular dilation via increasing TIMP levels

OBJECTIVE: Nuclear factor-kappa B (NF-kappaB) orchestrates genes involved in inflammation and extracellular matrix (ECM) remodeling following myocardial infarction (MI). The objective of the present study was to investigate the effect of overexpression and mode of function of IkappaB, the natural inhibitor of NF-kappaB, on ECM remodeling in a rat model of MI. METHODS: MI was induced in male Sprague-Dawley rats by ligation of the left anterior descending coronary artery (LAD) and was followed by adenovirus-mediated intramyocardial transfection of IkappaB (n = 26) or LacZ reporter genes (n = 26). Sham-operated animals (n = 14) served as controls. RESULTS: In transthoracic echocardiography 49 days after MI, systolic and diastolic left ventricular dimensions were reduced while fractional shortening was preserved in the treatment group. Additionally, evaluation on the isolated heart showed an attenuated downward shift of pressure-volume relationships in the IkappaB group compared to LacZ. NF-kappaB p65 DNA binding activity was diminished both at 5 and 49 days post-MI in the treatment group. Five days post-MI in the treatment group, protein levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were significantly reduced by 72.6% and 73.2%, respectively, compared to LacZ (p<0.05). In parallel, matrix metalloproteinase (MMP)-2 and MMP-9 levels were reduced 5 days post-MI, with MMP-9 still being decreased 49 days post-MI (p<0.01). In contrast, tissue inhibitors of metalloproteinases (TIMP)-1, -2, and -3 were increased compared to LacZ (p<0.01 and p<0.05, respectively) 5 days post-MI. After 49 days, TIMP-2, -3, and -4 expressions were significantly elevated (p<0.05). CONCLUSION: Reducing NF-kappaB activity via IkappaB overexpression after MI positively influences ECM remodeling by reducing MMP-2 and -9 levels while increasing TIMP-1, -2, -3, and -4 levels. Therefore, IkappaB overexpression prevents ventricular dilation and consequently preserves cardiac function.