OBJECTIVETo study the expression of serum cytokines, interleukin-38 (IL-38) and interleukin-1β (IL-1β) in the acute phase of Kawasaki disease (KD) in children and the association of IL-38 and IL-1β with inflammatory response in the acute phase and the development of coronary artery lesion (CAL).

METHODSA total of 40 children with KD who were hospitalized in the hospital between July 2015 and June 2016 were enrolled, with 21 children in the CAL group and 19 in the non-CAL (NCAL) group. Thirty healthy children and 19 children with infection and pyrexia, who were matched for sex and age, were enrolled as healthy control group and pyrexia control group respectively. ELISA was used to measure the serum levels of IL-38 and IL-1β in the 40 children in the acute phase of KD. Spearman's rank correlation analysis was used to investigate the correlations of IL-1β and IL-38 with interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), triglyceride (TG), and total cholesterol (TC).

RESULTSThe serum level of IL-38 in the children in the acute phase of KD was significantly lower than that in the healthy control group (P<0.05), but significantly higher than that in the pyrexia control group (P<0.05). There was no significant difference in the level of IL-38 between the CAL and NCAL groups (P>0.05). The children in the acute phase of KD had a significantly higher level of IL-1β than the healthy control group (P<0.05), while there was no significant difference between this group and the pyrexia control group (P>0.05). There was also no significant difference in the level of IL-1β between the CAL and NCAL groups (P>0.05). Serum IL-1β and IL-38 levels were not correlated with serum levels of CRP, ESR, PCT, IL-6, and NT-ProBNP or blood lipids (TG and TC) (P>0.05).

CONCLUSIONSIL-38 is involved in an inflammatory response in the acute phase of KD and may exert an anti-inflammatory effect, which is opposite to the effect of IL-1β to promote inflammatory response. However, there is no significant correlation between these two cytokines and the development of CAL in KD.

Acute Disease ; Atrial Natriuretic Factor ; blood ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Cholesterol ; blood ; Coronary Artery Disease ; blood ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Interleukin-1beta ; blood ; Interleukins ; blood ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; Procalcitonin ; blood ; Protein Precursors ; blood ; Triglycerides ; blood

BackgroundAcute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance.

MethodsA total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed.

ResultsThe levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively).

ConclusionsThe serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.

1-Alkyl-2-acetylglycerophosphocholine Esterase ; metabolism ; Acute Coronary Syndrome ; blood ; immunology ; metabolism ; Adult ; Aged ; Chitinase-3-Like Protein 1 ; metabolism ; Coronary Angiography ; Coronary Disease ; blood ; immunology ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Middle Aged

BACKGROUNDPercutaneous coronary intervention (PCI) causes endothelial damage, resulting in an inflammatory response with elevation of markers such as high-sensitive C-reactive protein (hs-CRP) and vascular cell adhesion molecule-1 (VCAM-1), which are associated with restenosis after PCI. Evidence suggests that microRNA-126 (miR-126) plays an important role in vascular inflammation, but its correlation with PCI-mediated inflammation has not been investigated. In this study, we investigated the effect of PCI on circulating miR-126 and inflammation markers such as hs-CRP and VCAM-1.

METHODSWe enrolled 130 patients with coronary artery disease (CAD) in the Second Hospital of Jilin University from October 2015 to December 2015. Among them, 82 patients with CAD, defined as at least one major epicardial vessel with >70% stenosis who planned to undergo PCI, were divided into acute coronary syndrome (ACS) group (46 patients) and stable angina (SA) group (36 patients). Forty-eight patients confirmed by coronary angiography without PCI were used as controls. The plasmas of all patients were collected prior to PCI and at 30 min, 24 h, and 72 h after PCI. The plasma VCAM-1 and hs-CRP were detected by enzyme-linked immunosorbent assay, and the miR-126 was evaluated by quantitative reverse transcription-polymerase chain reaction.

RESULTSPlasma concentrations of hs-CRP and VCAM-1 in patients with either ACS (n = 46) or SA (n = 36) were significantly higher than in controls (n = 48) (P < 0.01) prior to PCI, and increased further at 24 h and 72 h after PCI, compared with prior PCI. Moreover, VCAM-1 was positively correlated with balloon time and pressure. In contrast, the plasma concentration of miR-126 was significantly lower in patients with CAD than in controls, and further decreased with time post-PCI. A negative correlation was observed between miR-126 and hs-CRP and VCAM-1 at 72 h after PCI.

CONCLUSIONThere was a negative correlation of miR-126 with the PCI-induced markers of inflammation such as hs-CRP and VCAM-1.

Acute Coronary Syndrome ; blood ; Angina, Stable ; blood ; C-Reactive Protein ; metabolism ; Coronary Angiography ; Coronary Artery Disease ; blood ; surgery ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; MicroRNAs ; blood ; Middle Aged ; Percutaneous Coronary Intervention ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Cell Adhesion Molecule-1 ; blood

BACKGROUND/AIMS: Newer P2Y12 inhibitors, such as prasugrel and ticagrelor, have greater antiplatelet efficacy but may increase the risk of bleeding. In this study, we compared the pharmacodynamic efficacy of prasugrel and ticagrelor in East Asian patients with acute coronary syndrome (ACS). METHODS: We selected 83 ACS patients undergoing percutaneous coronary intervention who were discharged with 90 mg ticagrelor twice daily (n = 24), 10 mg prasugrel daily (n = 39) or 5 mg prasugrel daily (n = 20). After 2 to 4 weeks, on-treatment platelet reactivity (OPR) was assessed in terms of P2Y12 reaction units (PRUs) using the VerifyNow P2Y12 assay (Accumetrics). We compared East Asian (85 < PRU < or = 275) and Caucasian (85 < PRU < or = 208) criteria for assessing the therapeutic window of OPR. RESULTS: OPR was lowest in the ticagrelor group, followed by the 10 mg prasugrel and 5 mg prasugrel groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, respectively; p < 0.001). The 5 mg prasugrel group had the highest proportion of patients with OPR values within the therapeutic window, followed by the 10 mg prasugrel and ticagrelor groups (90.0% vs. 46.2% vs. 12.5%, respectively; p < 0.001 for East Asian criteria; 60.0% vs. 43.6% vs. 12.5%, respectively; p < 0.001 for Caucasian criteria). CONCLUSIONS: Short-term administration of 5 mg prasugrel facilitated maintenance within the therapeutic window of OPR compared with the 10 mg prasugrel and ticagrelor groups. Thus, 5 mg prasugrel daily may be the optimal antiplatelet regimen for stabilized East Asian ACS patients.
Acute Coronary Syndrome/blood/diagnosis/ethnology/*therapy ; Adenosine/administration & dosage/adverse effects/*analogs & derivatives/pharmacology ; Aged ; *Asian Continental Ancestry Group ; Blood Platelets/*drug effects/metabolism ; Drug Administration Schedule ; Drug Monitoring/methods ; European Continental Ancestry Group ; Female ; Hemorrhage/chemically induced ; Humans ; Male ; Middle Aged ; *Percutaneous Coronary Intervention/adverse effects ; Pilot Projects ; Platelet Aggregation Inhibitors/administration & dosage/adverse effects ; Platelet Function Tests ; Prasugrel Hydrochloride/administration & dosage/adverse effects/*pharmacology ; Purinergic P2Y Receptor Antagonists/administration & dosage/adverse effects/*pharmacology ; Receptors, Purinergic P2Y12/blood/*drug effects ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome

This study established a population pharmacokinetics-pharmacodynamics model of clopidogrel in patients with acute coronary syndrome. Fifty-nine patients were enrolled. The plasma concentration of clopidogrel active metabolite and vasodilator stimulated phosphoprotein platelet reactivity index (VASP-PRI) were selected as the pharmacokinetics index and the pharmacodynamics index, respectively. The covariates including demographic characteristics, laboratory indexes, combined medication, complications and genetic polymorphisms of related enzymes were screened for their influence on the pharmacokinetic and pharmacodynamics parameters. Population pharmacokinetic and pharmacodynamics data analysis was performed using NONMEM software. The general linear model and the indirectly effect model-turnover model for pharmacokinetic and pharmacodynamic analysis were selected as the basic model, respectively. The population typical values of K12, CL/F, V/F, EC50, K(in), and E(max) were 0.259 h(-1), 179 L x h(-1), 632 L, 1.57 ng x mL(-1), 4.29 and 0.664, respectively. CYP2C19 was the covariate in the final pharmacokinetic model, and the model was to design a prior dosage regimen.
Acute Coronary Syndrome ; metabolism ; Humans ; Polymorphism, Genetic ; Ticlopidine ; analogs & derivatives ; pharmacokinetics

PURPOSE: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) binds to low-density lipoprotein. The levels of Lp-PLA2 reflect the plaque burden, and are upregulated in acute coronary syndrome (ACS). We investigated the diagnostic value of Lp-PLA2 levels and found that it might be a potential biomarker for ACS. MATERIALS AND METHODS: We classified 226 study participants into three groups: patients without significant stenosis (control group), patients with significant stenosis with stable angina (SA group), and patients with ACS (ACS group). RESULTS: Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) levels were significantly greater in the ACS group than in the SA group (p=0.044 and p=0.029, respectively). Multivariate logistic regression analysis revealed that Lp-PLA2 levels are significantly associated with ACS (odds ratio=1.047, p=0.013). The addition of Lp-PLA2 to the ACS model significantly increased the global chi2 value over traditional risk factors (28.14 to 35.602, p=0.006). The area under the receiver operating characteristic curve for Lp-PLA2 was 0.624 (p=0.004). The addition of Lp-PLA2 level to serum hs-CRP concentration yielded an integrated discrimination improvement of 0.0368 (p=0.0093, standard error: 0.0142) and improved the ability to diagnose ACS. CONCLUSION: Lp-PLA2 levels are related to plaque stability and might be a diagnostic biomarker for ACS.
1-Alkyl-2-acetylglycerophosphocholine Esterase/*blood ; Acute Coronary Syndrome/*blood/physiopathology ; Aged ; Aged, 80 and over ; Angina Pectoris ; Biological Markers/blood ; C-Reactive Protein/*metabolism ; Coronary Angiography ; Female ; Humans ; Lipoproteins, LDL/*blood ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Plaque, Atherosclerotic/blood ; ROC Curve ; Risk Factors

OBJECTIVETo study the changes of adenosine diphosphate (ADP)-induced platelet aggregation rate, and evaluate the effects of Maixuekang Capsule (, MKC) on platelet aggregation rate and long-term prognosis of patients with acute coronary syndrome after percutaneous coronary intervention (PCI).

METHODSA total of 236 patients with acute coronary syndrome, who received successful PCI, were randomly assigned to a trial group (116 cases) and a control group (120 cases) according to random numbers; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent forms. In the trial group, the patients were treated with MKC combined with routine medication, and in the control group the patients were treated with routine medication. The therapeutic course for the two groups was 12 months and the follow-up was 12 months. The levels of ADP-induced platelet aggregation rate and serum high-sensitive C-reactive protein (hs-CRP) were determined before PCI, 12 h and 30 days after PCI. In the meantime, the incidence of cardio-/cerebrovascular events was recorded during the 12-month follow-up.

RESULTSCompared with before PCI, the levels of ADP-induced platelet aggregation rate and serum hs-CRP were significantly higher at 12 h after PCI (P<0.05). They were significantly reduced after 30-day-treatment of MKC, showing statistical differences when compared with those in the control group (P<0.05). During the 12-month follow-up, the incidence of cardio-/cerebrovascular events was significantly lower in the trial group than in the control group (6.9% vs. 12.5%, P<0.01).

CONCLUSIONSADP-induced platelet aggregation function was significantly elevated after PCI. MKC improved the prognosis of patients with acute coronary syndrome, possibly through inhibiting the platelet aggregation, fighting against inflammation, and protecting the vascular endothelial function.

Acute Coronary Syndrome ; drug therapy ; surgery ; Adenosine Diphosphate ; pharmacology ; Aged ; C-Reactive Protein ; metabolism ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Percutaneous Coronary Intervention ; Platelet Aggregation ; drug effects ; Prognosis

OBJECTIVETo explore effects of salvianolate on inflammatory cytokines (C-reactive protein, resistin, and adiponectin) of patients with acute coronary syndrome (ACS), and to analyze its possible treatment mechanisms for ACS patients.

METHODSEighty-three inpatients with ACS at the Cardiology Department of our hospital were randomly assigned to the treatment group and the control group from May 2011 to January 2012. Those in the treatment group (42 cases) were treated with routine Western medical treatment and intravenous injection of Salvianolate (200 mg/day), while those in the control group (41 cases) were treated with routine Western medical treatment. The therapeutic course for all was 14 days. The serum levels of resistin,adiponectin, and CRP were observed before and after treatment.

RESULTSCompared with before treatment, the serum levels of resistin and CRP significantly decreased, and the serum level of adiponectin significantly increased in the two groups after treatment (P < 0.05). Besides, the decrement of serum levels of resistin and CRP and the increment of serum adiponectin level were obviously higher in the treatment group than in the control group, showing statistical difference between the two groups (P <0.05).

CONCLUSIONSalvianolate could obviously reduce the serum levels of resistin and CRP, and increase the serum adiponectin lever; indicating that partial therapeutic effects of salvianolate might come from its anti-inflammation.

Acute Coronary Syndrome ; blood ; Adiponectin ; blood ; C-Reactive Protein ; metabolism ; Female ; Humans ; Inflammation ; Male ; Middle Aged ; Plant Extracts ; pharmacology ; Resistin ; blood

PURPOSE: The aim of this study was to demonstrate the early effects of statin treatment on plaque composition according to plaque stability on Intravascular Ultrasound-Virtual Histology at 6 months after a coronary event. Previous trials have demonstrated that lipid lowering therapy with statins decreases plaque volume and increases plaque echogenicity in patients with coronary artery disease. MATERIALS AND METHODS: Fifty-four patients (54 lesions) with acute coronary syndrome were prospectively enrolled. We classified and analyzed the target plaques into two types according to plaque stability: thin-cap fibroatheroma (TCFA, n=14) and non-TCFA (n=40). The primary end point was change in percent necrotic core in the 10-mm subsegment with the most disease. RESULTS: After 6 months of statin therapy, no change was demonstrated in the mean percentage of necrotic core (18.7+/-8.5% to 20.0+/-11.0%, p=0.38). There was a significant reduction in necrotic core percentage in patients with TCFA (21.3+/-7.2% to 14.4+/-8.9%, p=0.017), but not in patients with non-TCFA. Moreover, change in percent necrotic core was significantly correlated with change in high-sensitivity C-reactive protein levels (r=0.4, p=0.003). Changes in low-density lipoprotein cholesterol levels and lipid core percentage demonstrated no significant associations. CONCLUSION: A clear reduction of lipid core was observed only for the TCFA plaque type, suggesting that changes in plaque composition following statin therapy might occur earlier in vulnerable plaque than in stable plaque; the effect may be related to the anti-inflammatory effects of statins.
Acute Coronary Syndrome/*drug therapy/ultrasonography ; Aged ; C-Reactive Protein/metabolism ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Male ; Middle Aged ; Plaque, Atherosclerotic/*ultrasonography ; Ultrasonography, Interventional

The aim of this study was to investigate the tissue factor (TF) expression of platelets and leukocytes in patients with acute coronary syndrome (ACS), patients with stable angina (SA) and healthy subjects (as controls). 26 patients with ACS, 29 patients with SA, and 25 controls were enrolled in this study. The peripheral blood samples of above-mentioned subjects were collected and isolated to obtain the monocytes and platelet-rich plasma, the TF-mRNA expression of monocytes, and platelets among 3 groups was detected by RT-PCR, the TF expression ratio of platelets, platelet-leukocyte aggregates (PLA) and platelet-monocyte aggregates (PMP) was detected by flow cytometry among 3 groups. The results showed that the TF mRNA expression level of platelets in ACS group were significantly higher (3.11 ± 0.51 relative expression) as compared with SA and control groups (1.88 ± 0.78 and 0.7 ± 0.1, respectively) (P = 0.03). Expression of TF mRNA of monocytes was higher in ACS group (P = 0.05 versus controls) too. ACS group had a significantly higher amount of TF-positive platelets (8.8 ± 2.6) than SA (2.6 ± 0.5, P = 0.02) or control groups (2.5 ± 0.4, P = 0.02). A significantly greater number of TF positive platelet-leukocyte aggregates and platelet-monocyte aggregates were also found by flow cytometry in blood of ACS patients than in either SA patients or controls. It is concluded that the high TF expression of platelets and leukocytes in ACS patients strengthens the platelet activation, blood coagulation, and thrombus formation and may further contribute to the hypercoagulability associated with the disease. The present study further extends the proinflammatory/prothrombotic phenotype of ACS patients showing that new players on the scene.
Acute Coronary Syndrome ; blood ; Aged ; Angina, Stable ; blood ; Blood Platelets ; metabolism ; Case-Control Studies ; Cell Adhesion ; Female ; Humans ; Leukocytes ; metabolism ; Male ; Middle Aged ; Platelet Aggregation ; RNA, Messenger ; metabolism ; Thromboplastin ; metabolism