Acute Coronary Syndrome ; metabolism ; pathology ; physiopathology ; Cholesterol ; metabolism ; Erythrocyte Membrane ; metabolism ; Humans

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article.
Acute Coronary Syndrome/metabolism ; Arrhythmias, Cardiac/metabolism ; Heart Failure/*metabolism ; Humans ; Hypertension, Pulmonary/metabolism ; Natriuretic Peptides/*metabolism ; Sepsis/metabolism

Acute Coronary Syndrome ; enzymology ; C-Reactive Protein ; metabolism ; Humans ; Matrix Metalloproteinase 9 ; metabolism

Acute Coronary Syndrome ; blood ; Aged ; Cell Membrane ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Thromboplastin ; metabolism

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

OBJECTIVETo observe the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the unstable plaque of patients with acute coronary syndrome (ACS), and the impact of leukotriene B4 (LTB4) on the EMMPRIN expression in macrophages.

METHODSThe EMMPRIN expression was detected by immunohistochemistry in 11 unstable plaques from patients with ACS. Protein expression of EMMPRIN was evaluated by Western blot on macrophages differentiated from THP-1 which were stimulated with LTB4 in the absence or presence of LTB4 antagonist U75302. There are 8 study groups: 1-THP-1, 2-8-the macrophages derived from THP-1, 2-6-macrophages were stimulated by LTB4 (0, 10(-10), 10(-9), 10(-8) and 10(-7) mol/L) for 24 h, 7-8-the macrophages were pretreated by 10(-6) mol/L or 10(-7) mol/L U75302 2 h before the LTB4 (10(-7) mol/L) stimulation.

RESULTSAbundant EMMPRIN expression was detected in macrophages and smooth muscle cells of unstable plaques from ACS patients. As to the THP-1 derived macrophages, EMMPRIN expression was significantly upregulated in a concentration-dependent manner in LTB4 stimulated groups, which was significantly higher in group 3-6 than in the THP-1 group (group 1) and macrophages group (group 2) (all P < 0.05) and pretreatment with U75302 significantly reduced the LTB4 induced upregulation of EMMPRIN in a dose-dependent manner (P < 0.05).

CONCLUSIONEMMPRIN expression is enhanced in macrophages and smooth muscle cells on unstable coronary artery plaques from ACS patients. LTB4 could stimulate EMMPRIN expression on THP-1 derived macrophages suggesting that LTB4 and EMMPRIN might be both involved in the formation and progression of unstable plaques, future studies are warranted to explore if LTB4 and EMMPRIN antagonists are effective or not for treating patients with ACS.

Acute Coronary Syndrome ; metabolism ; pathology ; Basigin ; metabolism ; Cell Line ; Humans ; Leukotriene B4 ; metabolism ; pharmacology ; Macrophages ; drug effects ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Plaque, Atherosclerotic ; metabolism

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

OBJECTIVETo investigate the prognostic value of ultra-sensitive pregnancy associated plasma protein-A (PAPP-A) level in the early phase of acute coronary syndrome (ACS) attack.

METHODSPatients diagnosed as ACS were enrolled and the level of circulatory PAPP-A was measured within 12 hours after ACS attack. The patients were followed at the time of 1st, 6th, and 12th months post-ACS attack in order to observe the incidence of the cardiovascular adverse events. According to the highest quintile, the patients were divided into 2 groups: high level (≥26.08 μg/L) group and low level (<26.08 μg/L) group, to evaluate the association between the level of PAPP-A and the incidence of the cardiovascular events.

RESULTSCompared with the low level group, the incidence of the composite outcome is significantly increased in the high level group, and the values of OR are 4.76, 4.38, 3.75 for 1st, 6th, 12th months respectively (P=0.000). For myocardial infarction (MI) + cardiac death (CD) the values of OR were 9.81, 6.08, 4.12 (P<0.01). Multivariate logistic regression analysis demonstrates that PAPP-A was an independent risk factor for the cardiovascular adverse events in the early, median, and late phase of ACS (P<0.05).

CONCLUSIONIn the early phase of ACS attack, the elevation of PAPP-A is an independent risk factor for the occurrence of cardiovascular adverse events.

Acute Coronary Syndrome ; blood ; diagnosis ; Aged ; Female ; Humans ; Male ; Middle Aged ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Prognosis ; Risk Factors

OBJECTIVETo explore the relationship between serum apolipoprotein A5 (ApoA5) and lipid profile or high sensitive C-reactive protein (hs-CRP) in patients with acute coronary syndrome (ACS).

METHODSSerum apoA5 and hs-CRP levels were measured by ELISA and immunoturbidimetry in control subjects (n = 232), patients with stable angina (SA, n = 127), unstable angina (UA, n = 116) and acute myocardial infarction (AMI, n = 112). Triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were also measured.

RESULTSCompared with controls [(108.7 +/- 23.2) microg/L] and SA patients [(78.3 +/- 20.2) microg/L], serum ApoA5 level was significantly increased in UA [(340.6 +/- 63.5) microg/L] and AMI patients [(373.2 +/- 73.8) microg/L] (all P < 0.05). ApoA5 was positively correlated with TG (r = 0.63 and 0.67, respectively, all P < 0.05) and hs-CRP (r = 0.57 and 0.55, respectively, all P < 0.05) in UA and AMI patients but there were no significant correlations between ApoA5 and TC, HDL-C and LDL-C in ACS patients (all P > 0.05).

CONCLUSIONIncreased serum apoA5 level and the positive correlation between ApoA5 and serum TG and hs-CRP in ACS patients might reflect increased inflammation responses in ACS patients.

Acute Coronary Syndrome ; blood ; Aged ; Apolipoprotein A-V ; Apolipoproteins A ; blood ; C-Reactive Protein ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Triglycerides ; blood

OBJECTIVETo investigate the changes of neutrophil myeloperoxidase (MPO) blood concentration gradient between the systemic circulation and the coronary circulation among patients with acute coronary syndrome and its clinical value.

METHODSFifty patients underwent coronary angiography, which including 10 patients in AMI group, 20 patients in UA group, 10 patients in SA group and 10 subjects served as control. The levels of MPO and hs-CRP were measured in the serum of blood collected from femoral vein, aortic artery root and coronary sinus.

RESULTSCompared with the control, concentrations of LDL in the AMI, UA and SA groups were significantly increased, while the latter three groups did not differ from each other. In the UA patients, the in-gate percentage of MPO decreased in the coronary sinus compared with that in the root of aortic artery (P < 0.01); the in-gate percentage of MPO decreased through coronary circulation more than through systemic circulation (P < 0.001); the average fluorescent intensity of MPO and the concentrations of hs-CRP showed no difference between samples from the coronary sinus and that from the root of aortic artery. In the AMI patients, the average fluorescent intensity of MPO in the coronary sinus was weakened compared with that in the root of aortic artery (P < 0.05); it decreased through coronary circulation more than through systemic circulation (P < 0.001); neither the in-gate percentage of MPO nor the concentrations of hs-CRP showed significant difference between samples from the coronary sinus and that from the root of aortic artery. In the control and SA groups, samples from the femoral vein, the root of aortic artery, and the coronary sinus did not show differences at the serum level of MPO and hs-CRP. In the UA group, the in-gate percentage of MPO correlated positively with the concentration of hs-CRP (r = 0.78, P < 0.01), and with the level of LDL as well (r = 0.52, P < 0.05); In the AMI group, the average fluorescent intensity of MPO correlated negatively with the concentration of hs-CRP (r = -0.80, P < 0.01), and showed no correlation with the level of LDL (r = 0.22, P > 0.05).

CONCLUSIONSMPO is a better marker for inflammation of the local plaques. It may be one of the mechanisms that MPO induces the transforming from LDL to ox-LDL in plaques vulnerability.

Acute Coronary Syndrome ; blood ; metabolism ; physiopathology ; Aged ; Biomarkers ; blood ; Case-Control Studies ; Coronary Circulation ; Female ; Humans ; Male ; Middle Aged ; Neutrophils ; enzymology ; Peroxidase ; blood