Pathogenesis Of Acute Coronary Syndromes Research Articles

Is IL-10 a predictor of in-stent restenosis in stable and unstable angina patients undergoing coronary interventions?

Inflammation is an important feature of atherosclerotic lesions and associated with the pathogenesis of acute coronary syndromes (ACS) and the development of restenosis after coronary angioplasty (PCI) [1–3].

Inflammation and its resolution as determinants of acute coronary syndromes.

Inflammation contributes to many of the characteristics of plaques implicated in the pathogenesis of acute coronary syndromes. Moreover, inflammatory pathways not only regulate the properties of plaques that precipitate acute coronary syndromes but also modulate the clinical consequences of the thrombotic complications of atherosclerosis. This synthesis will provide an update on the fundamental mechanisms of inflammatory responses that govern acute coronary syndromes and also highlight the ongoing balance between proinflammatory mechanisms and endogenous pathways that can promote the resolution of inflammation. An appreciation of the countervailing mechanisms that modulate inflammation in relation to acute coronary syndromes enriches our fundamental understanding of the pathophysiology of this important manifestation of atherosclerosis. In addition, these insights provide glimpses into potential novel therapeutic interventions to forestall this ultimate complication of the disease.

The 14 bp Del/Ins HLA-G Polymorphism Is Related with High Blood Pressure in Acute Coronary Syndrome and Type 2 Diabetes Mellitus

Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P ≥ 0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (ORc = 1.65, P = 0.02). The genetic recessive model showed similar findings (ORc = 3.03, P = 0.04). No association was found in ACS, with a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups.

Abstract 9508: Neutrophil to Lymphocyte Ratio Predicts Short and Long Term Mortality After Revascularized ST Elevation Myocardial Infarction

Introduction: Several biomarkers of inflammation have been implicated in the pathogenesis of acute coronary syndromes. The role of inflammatory markers in predicting short and long term survival after revascularized STEMI remains poorly defined. Patient and methods: We retrospectively evaluated 250 consecutive STEMI patients admitted to a tertiary care center over one year. Exclusion criteria included:acute sepsis, trauma, recent surgery or underlying malignancy. Data analyzed included demographics, clinical presentation, leukocyte markers, electrocardiograms, therapy and major adverse cardiac events. Results: Mean age was 62±15 years, 70.4% subjects were males, almost equal number were Caucasians (49.4%) and non-Caucasians with mean follow up of 571±291 (Median=730) days. Considering available inflammatory markers, univariate predictors of mortality included only White Cell Count (14.52±8.09*10 3 /microliter;p<0.001) and neutrophil to lymphocyte ratio [NLR] (9.12±8.75;p=0.011). Multivariate regression analysis of all univariate predictors revealed NLR (OR=2.64;p=0.026), female gender (OR=5.35;p<0.001), cerebrovascular accident history (OR=3.36;p=0.023), low glomerular filtration rate (OR=0.98;p=0.012) and cardiac arrest on admission (OR=17.43;p<0.001) as independent predictors of 2-year mortality. NLR was subdivided based on an optimal cut off value (OCV) of 7.4, when combined with Thrombolysis in Myocardial Infarction (TIMI) Score provided the highest predictive power for mortality with Area Under the Curve (AUC) of 0.799 (95 CI:0.734,0.865;p<0.001). Short term (30 days) and long term (2-years) mortality stratified by NLR (Figure 1-A) and Kaplan Meier survival analysis (Figure 1-B) are illustrated. Conclusion: NLR based on OCV of 7.4 is an excellent predictor of short and long term survival with additive prognostic value to conventional clinical and angiographic scoring systems used for revascularized STEMI patients.

Association of P-selectin glycoprotein ligand-1 and pathogenesis of acute coronary syndrome assessed by optical coherence tomography

Association of P-selectin glycoprotein ligand-1 and pathogenesis of acute coronary syndrome assessed by optical coherence tomography

GW24-e1722 FOXP3 demethylation as a means of identifying quantitative defects in regulatory T cells in acute coronary syndrome

ObjectivesThe contribution of regulatory T cells (Tregs) to the pathogenesis of acute coronary syndrome (ACS) remains poorly understood. One core obstacleis the lack of Treg-specific markers. A highly conserved CpG...

FOXP3 demethylation as a means of identifying quantitative defects in regulatory T cells in acute coronary syndrome

ObjectiveThe contribution of regulatory T cells (Tregs) to the pathogenesis of acute coronary syndrome (ACS) remains poorly understood. One core obstacle is the lack of Treg-specific markers. A highly conserved CpG enriched element in forkhead box P3 intron 1 (FOXP3 i l) is unmethylated only in Tregs, and measuring the unmethylation of FOXP3 i l can be used to identify the role of Tregs in clinical diseases. This study investigated whether analyzing the demethylation status of FOXP3 i 1 is a more reliable means than using Treg-specific surface markers in ACS. Methods and resultsWe evaluated circulating Tregs percentages on different levels including cell frequencies (CD4+CD25hiFOXP3+Tregs and CD4+CD25hiCD45+naïve Tregs) or FOXP3 mRNA, FOXP3 i 1 demethylation status and related cytokine secretion in 89 patients with ACS and 35 controls. FOXP3 i 1 demethylation assay showed that the amount of Tregs in ACS patients was significantly reduced than that in controls (p = 0.0005). However, flow cytometry analysis did not identify any reduction of CD4+CD25hiFOXP3+Tregs in ACS patients. Notably, younger patients had higher percentage of CD4+CD25hiFOXP3+Tregs but decreased percentage of CD4+CD25hiCD45+naïve Tregs than either controls or older patients. Furthermore, a DNA hypomethylation agent increased the amount of CD4+CD25hiFOXP3+Tregs and Tregs related cytokine IL-10 and suppressed the production of pro-inflammatory cytokine interferon-γ by inducing FOXP3 i 1 demethylation in vitro. ConclusionsA quantitative defect of Tregs, suggestive of decreased peripheral tolerance, could be a potential hallmark of ACS disease. Targeting FOXP3 i l demethylation might elevate the inhibitory activity of Tregs in ACS.

ASSOCIATION OF ANTI-PHOSPHATIDYLCHOLINE ANTIBODIES WITH ACUTE MYOCARDIAL INFARCTION: A COMPARATIVE STUDY

Many factors play a role in Acute Myocardial Infarc tion (AMI). One those anti-Phospholipid (aPL) antibodies, that may act in the induction of immuno logical response leading to the development of AMI. Anti-Phosphatidylcholines (PC) antibody is detected in various diseases like rheumatoid arthritis, systemic lupus erythematosus and anti-phospholipid antibody syndrome. The study of anti-PC antibody in AMI might shed light on etiologic mechanisms in the pathogenesis of acute coronary syndromes. This study was designed to investigate whether prev alence of anti-PC antibodies, in patients who had AMI and to analyze their relationship with traditio nal cardiovascular risk factors. The prevalence of anti-PC IgG and IgM in a well characterized group o f patients with AMI as a case group and in age and sex matched healthy subjects as control group. Sera from the case and the control groups were tested to evaluate the presence of IgG and IgM isot ypes to anti-PC by ELISA method. The prevalence of anti-PC IgG and also IgM in the case group resul ted significantly higher than in the control group with AMI (p<0.005). Our findings suggest that anti- PC antibodies seemed to play a role in AMI, independent risk factors for AMI, which may represe nt a link between autoimmunity and atherosclerosis in patients with AMI. Further studi es with bigger sample size including patients with AMI and healthy people are needed to explore the ex act role of anti-PC antibodies in AMI.

ASSA13-01-13 FOXP3 Demethylation as a Means of Identifying Quantitative Defects in Regulatory T Cells in Acute Coronary Syndrome

<h3>Background</h3> The contribution of regulatory T cells (Tregs) to the pathogenesis of acute coronary syndrome (ACS) remains poorly understood. One core obstacle is the lack of Treg-specific markers that distinguish Tregs and activated conventional T cells. A highly conserved CpG enriched element in forkhead boxP3intron 1 (FOXP3 i l) is unmethylated only in Tregs, and measuring the unmethylation of FOXP3 i l can be used to identify the role of Tregs in clinical diseases. For this reason, we investigated whether analysing the demethylation status of FOXP3 i 1 is a more reliable means than using Treg-specific surface markers. <h3>Methods and Results</h3> Circulating Tregs percentages, cytokine (anti-inflammatory cytokines, IL-10 and TGF-β1; pro-inflammatory cytokine, interferon-γ) production profile in subjects with acute coronary syndrome (ACS) were correlated to the amount of FOXP3 protein expression measured by flow cytometry or FOXP3 mRNA expression measured by RT-PCR or FOXP3 i 1 demethylation status measured by pyrosequencing. Activated T cells were treated in vitro with a DNA demethylation agent to study the effect of DNA methylation on FOXP3 expression, FOXP3 i l demethylation and Treg cytokine production. FOXP3 i 1 demethylation assay showed that the amount of Tregs in ACS patients was significantly reduced than that in healthy controls (<i>p</i> = 0.0005). This test displayed a sensitivity of 94.7% and specificity of 80% in distinguishing ACS patients from healthy controls, as indicated by analysis of the receiver operating characteristic (ROC) curve (AUC = 0.916; <i>p</i> &lt; 0.001). However, flow cytometry analysis did not identify any reductions in total percentage of CD4⁺CD25⁺FOXP3⁺Tregs, indicating that CD4⁺CD25⁺FOXP3⁺Tregs in ACS patients were highly variable. Notably, younger patients with ACS had higher percentage of total CD4⁺CD25⁺FOXP3⁺Tregs but decreased percentage of CD4⁺CD25⁺CD45⁺naïve Tregs, higher amounts of interferon-γ, and lower amounts of high-density lipoprotein than either healthy controls or older patients with ACS. Furthermore, 5-aza-2′-deoxycytidine, a DNA hypomethylation agent, increased the amount of CD4⁺CD25⁺FOXP3⁺Tregs and IL-10 and suppressed the production of interferon-γ by inducing FOXP3 i 1 demethylation in vitro. <h3>Conclusions</h3> Our findings showed that a quantitative defect of Tregs, suggestive of decreased peripheral tolerance, could be a potential hallmark of ACS disease. Targeting FOXP3 i l demethylation might elevate the inhibitory activity of Tregs in ACS.

Association Among Leukocyte Count, Mortality, and Bleeding in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes (from the Acute Catheterization and Urgent Intervention Triage StrategY [ACUITY] Trial)

Although inflammation is involved in the pathogenesis of acute coronary syndromes, the extent of inflammation is not routinely assessed, and its prognostic implications in patients with non-ST-segment elevation acute coronary syndrome have not been investigated in depth. We analyzed the prognostic implications of an elevated white blood cell count (WBCc) in patients with moderate and high-risk non-ST-segment elevation acute coronary syndrome undergoing an early invasive strategy in the large-scale Acute Catheterization and Urgent Intervention Triage StrategY trial. The WBCc at admission was available for 13,678 of 13,819 patients (98.9%). The patients in the upper tertile of the WBCc had an increased risk of 30-day major bleeding, 1-year mortality, and definite/probable stent thrombosis compared to those in the mid or lower tertiles. On multivariate analysis, the WBCc was an independent predictor of 30-day major bleeding and 1-year cardiac, noncardiac, and all-cause mortality. The association between the WBCc and cardiac mortality was present in multiple prespecified subgroups, with no significant interaction between the WBCc and age, gender, diabetes, smoking, renal dysfunction, elevated baseline biomarkers, antithrombotic therapy, revascularization, and Thrombolysis In Myocardial Infarction risk score. The WBCc remained an independent predictor of mortality after adjusting for bleeding, C-reactive protein level, and angiographic variables, including left ventricular ejection fraction, Thrombolysis In Myocardial Infarction flow, and number of diseased vessels. The WBCc significantly improved the prognostic accuracy of the Thrombolysis In Myocardial Infarction risk score, with a net reclassification improvement of 11% (p <0.0001). In conclusion, in patients with moderate- and high-risk non-ST-segment elevation acute coronary syndrome, an elevated admission WBCc was an independent predictor of 30-day major bleeding, and 1-year cardiac, noncardiac, and all-cause mortality.

Effect of PSI‐697, a Novel P‐Selectin Inhibitor, on Platelet–Monocyte Aggregate Formation in Humans

BackgroundPlatelet activation is central to the pathogenesis of acute coronary syndromes. Surface expression of P‐selectin on activated platelets induces formation of platelet–monocyte aggregates and promotes vascular inflammation and thrombosis. P‐selectin antagonism may represent a novel therapeutic strategy in vascular disease. We aimed to investigate the effects of the novel P‐selectin antagonist PSI‐697 on platelet–monocyte aggregate formation in humans.Methods and ResultsIn a double‐blind, randomized, placebo‐controlled crossover study, healthy smokers were randomized to receive either oral PSI‐697 600 mg or matched placebo. The sequence of treatment was also randomized, with all subjects receiving both PSI‐697 and placebo. Platelet–monocyte aggregates were measured by flow cytometry at 4 and 24 hours in the presence and absence of thrombin receptor‐activating peptide (TRAP; 0.1 to 1.0 μm/L). The ex vivo addition of TRAP caused a concentration‐dependent increase in platelet–monocyte aggregates from 8.2% to 94.8% (P<0.001). At 4 and 24 hours, plasma concentrations of PSI‐697 increased to 1906 and 83 ng/mL, respectively (P<0.001). PSI‐697 had no demonstrable effect on either stimulated or unstimulated platelet–monocyte aggregates at 4 or 24 hours (P>0.05). P‐selectin‐blocking antibody (CLB‐Thromb6), but not PSI‐697, inhibited both stimulated and unstimulated platelet–monocyte aggregate formation in vitro (P<0.001).ConclusionsThe novel small‐molecule P‐selectin antagonist PSI‐697 did not inhibit basal or stimulated platelet–monocyte aggregate formation in humans at the dose tested. Its clinical efficacy remains to be established.Clinical Trial RegistrationURL: http://EudraCT.ema.europa.eu Unique identifier: 2007‐005695‐14.

Genome-Wide Association Study of Platelet Function in African Americans

AbstractAbstract 1068 Background:We have previously shown that platelet aggregation, an essential component of pathogenesis of acute coronary syndromes, has higher heritability in African Americans than Caucasians. However, a genome-wide association study of native platelet function in African Americans has not been reported. Methods:Platelet-rich plasma (PRP) was isolated from blood samples obtained from the discovery (GeneSTAR, N=835) and replication (Platelet Genes and Physiology Study, N=119) cohorts. Optical aggregation was used to measure maximal aggregation in PRP after samples were stimulated with arachidonic acid, collagen, ADP, or epinephrine. Genotyping was conducted with Illumina 1M arrays. For each cohort, age- and sex-adjusted linear mixed models were used to test for association between each SNP and each phenotype under an additive model. Results:Of the 117 SNPs that were significant (P< 5 × 10−8) in the discovery sample, 50 SNPs in 4 regions were also significant in the replication sample (Table). Among the replicated SNPs, a previously reported SNP in European Americans, rs12041331, in the PEAR1 gene was associated with ADP- and epinephrine-mediated aggregation. 47 SNPs in the 17q21.31 region, in one LD block, were associated with collagen-mediated aggregation. Conclusions:In this first GWAS of native agonist-mediated platelet aggregation in African Americans, we have discovered, and replicated in an independent sample, 4 regions that are associated with platelet aggregation. Several genes in the identified regions are expressed in platelets and further study of these genes may provide novel insights in platelet biology.Most significant SNPs associated with native platelet aggregation in the discovery and replication cohortsSNP (MA)Chr:PositionGeneFunctionMAF-GSMAF-PGAPPhenoES, P (GS)ES, P (PGAP)rs12041331(A)1:155136338PEAR1Intron38%32%ADP−9.2, 5.8 × 10−9−6.5, 0.03Epi−17.9, 8.3 × 10−17−14.7, 0.001rs11202221(G)10:8592294BMPR1Aintron8%9%ADP−12.7, 4.8 × 10−8−16.4, 2.4 × 10−5rs1800547(G)17:41407682MAPTintron6%7%Col0.09, 7.8 × 10−102.5, 0.03rs7216411(C)17:434439435%6%Col0.99, 5.4 × 10−172.7, 0.03Abbreviations: MA = minor allele; MAF = minor allele frequency; GS = GeneSTAR; PGAP = Platelet Genes and Physiology Study; ES = effect size; P = p-value. Disclosures:No relevant conflicts of interest to declare.

C-reactive protein induces expression of matrix metalloproteinase-9: A possible link between inflammation and plaque rupture

Matrix metalloproteases (MMPs) have been implicated in the pathogenesis of acute coronary syndromes (ACS). However, little is known about the mechanisms responsible for MMP expression in ACS. C-reactive protein (CRP) not only is an independent risk factor for cardiovascular events, but also may exert direct pro-atherosclerotic effects. Therefore, we aimed at determining whether CRP might induce MMP-9 in two different experimental conditions: 1) smooth muscle cells (SMCs) in vitro, and 2) patients with ACS. Effects of increasing concentrations of CRP on MMP-9 expression were evaluated in vitro in human SMCs. TIMP-1 protein expression, the selective inhibitor of MMP-9, was also evaluated. CRP dose-dependently induced MMP-9 expression in SMCs by promoting MMP-mRNA transcription, as well as MMP-9 secretion. In contrast, no differences were found for TIMP-1 protein expression. In vivo, MMP-9 and CRP levels were measured in blood samples obtained from the aorta (Ao) and the coronary sinus (Cs) of patients with normal coronary arteries (controls, n=21), stable angina (n=24), and ACS (n=30). Both MMP-9 and CRP plasma levels were significantly increased across the coronary circulation only in patients with ACS. Interestingly, a significant correlation between MMP-9 and CRP plasma levels was found. CRP induced MMP-9 expression and activity in human SMCs in culture; patients presenting with ACS have increased transcoronary plasma levels of MMP-9 and CRP with a significant correlation between these two markers. This may explain the heightened risk of coronary events in subjects with elevated levels of CRP.

CORRELATIVE STUDY BETWEEN THE LEVEL OF APELIN IN SERUM AND GENSINI SCORE IN PATIENTS WITH ACUTE CORONARY SYNDROME

ObjectivesSerum Ghrelin was measured in patients of acute coronary syndrome (ACS). Investigate whether serum levels of Ghrelin are associated with the Gensini score on patients with ACS.Methods75 cases of patients...

SERUM SOLUBLE CD137: RISK PREDICTION AFTER ACUTE CORONARY SYNDROMES

ObjectivesIncreasing evidence shows that CD137 plays an important role in the pathogenesis of acute coronary syndromes (ACS). This study evaluate the clinical predictive value of increased serum soluble CD137 (sCD137)...

A combination of increased Rho kinase activity and N-terminal pro-B-type natriuretic peptide predicts worse cardiovascular outcome in patients with acute coronary syndrome

BackgroundRecent experimental evidence suggests that the Rho/Rho-kinase (ROCK) system may play an important role in the pathogenesis of acute coronary syndrome (ACS) but there are little clinical data. This study examined if ROCK activity is increased in patients with acute coronary syndrome and if ROCK activity predicts long‐term cardiovascular event. MethodBlood samples were collected from 188 patients within 12h after admission for ACS (53% men; aged 70±13) and from 61 control subject. The main outcome measures were all cause mortality, readmission with ACS or congestive heart failure (CHF) from presentation within around 2years (mean:14.4±7.2months; range: 0.5 to 26months). ResultsROCK activity increased in ST elevation myocardial infarction (STEMI, n=90) (3.33±0.93), non-STEMI (NSTEMI, n=68) (3.37±1.04) and unstable angina (UA, n=30) (2.53±0.59) groups when compared with disease controls (n=31) (2.06±0.38, all p<0.001) and healthy controls (n=30) (1.54±0.43, all p<0.001). There were 24 deaths, 34 readmissions with ACS and 15 admissions with CHF within 2years. Patients with a high N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high ROCK activity on admission had a five-fold risk of a cardiovascular event (RR: 5.156; 95% CI: 2.180–12.191) when compared to those with low NT-proBNP and low ROCK activity. ConclusionROCK activity was increased in patients with ACS, particularly in those with myocardial infarction. The combined usage of both ROCK activity and NT-proBNP might identify a subset of ACS patients at particularly high risk.

Acute Coronary Syndromes as Auto-Inflammatory Disorders

From the onset to the healing stage of acute coronary syndromes, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Even though the early reperfusion treatment either by thrombolysis or percutaneous coronary intervention provides the excellent clinical benefits in patients with acute coronary syndromes, ischemia/ reperfusion injury may somewhat offset those great advantages. Inflammation, although potentially protective, has been deeply associated with those detrimental conditions. The hexagonal vascular inflammatory network which is composed of activated various leukocytes, vascular endothelial cells, vascular smooth muscle cells, platelets, excess reactive oxygen species, and cholesterol may contribute these vicious circles. To address these complex syndromes with more benefits regarding the prevention and treatment, this review comprehensively updates the pathogenesis of acute coronary syndromes from the view points of vascular inflammation.

High incidence of provoked coronary spasm in the presence of a stent after myocardial infarction

Coronary spasm is implicated in the pathogenesis of acute coronary syndromes including acute myocardial infarction (AMI). Stent implantation in the primary percutaneous coronary intervention is the first choice of treatment for patients with AMI. However, the relationship between coronary spasm and stent implantation after AMI and its clinical implications remain unknown. We examined the incidence and clinical implications of provoked coronary spasm after stent implantation in patients with AMI. Fifty-seven patients (43 men and 14 women with a mean age of 65.1±12.5 years) with ST elevation AMI who had undergone a stent implantation were the participants of this study. They underwent a provocation test for coronary spasm by intracoronary injection of acetylcholine 2-5 weeks after the attack. The patients with provoked spasms were given calcium channel blockers, and all the participants of the study were followed up for an average of 35.0±26.9 months. Coronary spasm was induced in 40 (70.2%) and multivessel spasm in 17 (29.8%) of the 57 patients. Spasms occurred in 31 (55.4%) of the infarct-related arteries (IRAs) and 33 (30.6%) of the non-IRAs. There was no significant difference (χ=1.01, P=0.314) in the major cardiac events between the spasm group and nonspasm group during the follow-up. Coronary spasm was provoked with a high frequency in both the IRAs and non-IRAs after stent implantation in patients with AMI. Calcium channel blockers may be useful to improve the prognosis in patients with AMI after stent implantation by suppressing coronary spasm.

Current Oral Antiplatelets: Focus Update on Prasugrel

Platelet activation and aggregation plays an integral role in the pathogenesis of acute coronary syndrome (ACS). The mainstay of ACS treatment revolves around platelet inhibition. It is known that greater platelet inhibition results in better ischemic outcomes; hence, focus in drug development has been to create more potent inhibitors of platelet aggregation. Prasugrel, a potent, third-generation thienopyridine, was approved by the US Food and Drug Administration in July 2009 for its use in ACS and percutaneous coronary intervention. The addition of prasugrel to aspirin for dual antiplatelet therapy has been shown to reduce the ischemic outcomes compared with clopidogrel and aspirin in combination. However, being a more potent antiplatelet agent, prasugrel increases the risk of bleeding, especially in those patients who are at a higher risk of bleeding complications. Elderly patients ≥75 years, patients who weigh ≥60 kg, and patients with a history of stroke or transient ischemic attack are at a higher risk of bleeding complications when prasugrel is used in combination with aspirin. Newer antiplatelets currently are being clinically evaluated to assess their efficacy in reducing ischemic events without increasing the bleeding risk.

Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention

1. Inflammation is central to the pathogenesis of acute coronary syndrome (ACS) and is associated with adverse clinical outcomes after percutaneous coronary intervention (PCI). Recent in vitro work has demonstrated the anti-inflammatory effect of berberine, a primary component of the traditional Chinese medicine 'umbellatine'. In the present study, we further tested whether berberine had any beneficial effects on ACS patients following PCI. 2.In all, 130 ACS patients undergoing PCI were recruited to the present study. Sixty-one patients were treated with berberine (300mg, t.i.d., for 30days) in addition to standard therapy, whereas the remaining patients received standard therapy alone. Circulating inflammatory markers were measured by ELISA, whereas serum lipid profiles were measured by routine chemical assays. 3.In the berberine-treated group, matrix metalloproteinase (MMP)-9, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, C-reactive protein, interleukin-6 and monocyte chemoattractant protein-1 were significantly reduced relative to baseline values. Furthermore, the changes in MMP-9, ICAM-1 and VCAM-1 from baseline to after 1month of treatment differed significantly between the two patient groups. There was a tendency for berberine to induce a slightly greater reduction in low-density lipoprotein cholesterol and triglycerides than standard therapy alone, without affecting high-density lipoprotein cholesterol, but the differences failed to reach statistical significance. No severe adverse effects of berberine were observed. 4.The results of the present study provide the first clinical evidence of the anti-inflammatory action of berberine in ACS patients following PCI. Berberine may become adjunct therapy to further improve clinical outcomes via its anti-inflammatory effect in ACS patients.