IL-17A facilitates platelet function through the ERK2 signaling pathway in patients with acute coronary syndrome

Background

Platelet aggregation mediated by inflammation played a critical role in the development of coronary heart diseases (CHD). Our previous clinical researches showed that Th17 cells and their characteristic cytokine IL-17A were associated with the plaque destabilization in patients with acute coronary syndrome (ACS). However, the potent effect of IL-17A on platelets-induced atherothrombosis remains unknown.

Methods and Results

In this study, we detected the plasma IL-17A levels and platelet aggregation in patients with stable angina (SA), unstable angina (UA), acute myocardial infarction (AMI) and chest pain syndrome (CPS). In addition, the markers of platelet activation (CD62P/PAC-1) and the mitogen-activated protein kinases (MAPKs) pathway were detected in platelets from ACS patients. We found that plasma IL-17A levels and platelet aggregation in patients with ACS (UA and AMI) were significantly higher than patients with SA and CPS, and the plasma IL-17A levels were positively correlated with the platelet aggregation (R = 0.47, P<0.01). In addition, in patients with ACS, the platelet aggregation, CD62P/PAC-1 and the phosphorylation of ERK2 signaling pathway were obviously elevated in platelets pre-stimulated with IL-17A in vitro. Furthermore, the specific inhibitor of ERK2 could attenuate platelet aggregation and activation triggered by IL-17A.

Conclusion

Our experiment firstly proved that IL-17A could promote platelet function in patients with ACS via activating platelets ERK2 signaling pathway and may provide a novel target for antiplatelet therapies in CHD.     

Current discharge management of acute coronary syndromes: data from the Rijnmond Collective Cardiology Research (CCR) study

Background

Medical discharge management of acute coronary syndromes (ACS) remains suboptimal outside randomised trials and constitutes an essential quality benchmark for ACS. We sought to evaluate the rates of key guideline-recommended pharmacological agents after ACS and characteristics associated with optimal treatment at discharge.

Methods

The Rijnmond Collective Cardiology Research (CCR) registry is an ongoing prospective, observational study in the Netherlands that aims to enrol 4000 patients with ACS. We examined discharge and 1-month follow-up medication use among the first 1000 patients enrolled in the CCR registry. Logistic regression was performed to identify patient and hospital characteristics associated with collective guideline-recommended pharmacotherapy at hospital discharge.

Results

At discharge, 94 % of patients received aspirin, 100 % thienopyridines, 80 % angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers, 87 % β-blockers, 96 % statins, and 65 % the combination of all 5 agents. ST-segment elevation myocardial infarction, hypertension, hypercholesterolaemia, and enrolment in an interventional centre were positive independent predictors of 5-drug combination therapy at discharge. Negative independent predictors were unstable angina and advanced age.

Conclusion

Current data from the CCR registry reflect a high quality of care for ACS discharge management in the Rotterdam-Rijnmond region. However, potential still remains for further optimisation.     

Serum tryptase detected during acute coronary syndrome is significantly related to the development of major adverse cardiovascular events after 2?years

Background

One of the greatest challenges in cardiovascular medicine is to define the best tools for performing an accurate risk stratification for the recurrence of ischemic events in acute coronary syndrome (ACS) patients.

Methods

We followed 65 ACS patients enrolled in a previous pilot study for 2 years after being discharged, focusing on the occurrence of major adverse cardiovascular events (MACE).The relationship between serum tryptase levels on admission, SYNergy between percutaneous coronary intervention with the TAXUS drug-eluting stent and the cardiac surgery score (SX-score), cardiovascular complexity and MACE at 2 years follow-up were analyzed.

Results

The ACS population was divided in two groups: patients with MACE (n = 23) and patients without MACE (n = 42).The tryptase measurement at admission (T0) and at discharge (T3) and SX-score were higher in patients who experienced MACE than in those without (p = 0.0001, p < 0.0001 and p = 0.006, respectively). Conversely, we found no significant association between MACE and C-reactive protein (CRP), and between MACE and maximum level of high-sensitivity troponin (hs-Tn) values.Among all patients with MACE, 96% belonged to the group that presented with cardiovascular complexity at the beginning of ACS index admission (p < 0.0001).The predictive accuracy of serum tryptase for MACE at follow up set at the cut-off point of 4.95 ng/ml at T0 and of 5.2 ng/ml at T3. Interestingly, patients with both the above cut-off tryptase values at T0 and at T3 presented a 1320% increase in the odds of developing MACE (p < 0.0001).

Conclusion

In ACS patients, serum tryptase measured during index admission is significantly correlated to the development of MACE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.

Electronic supplementary material

The online version of this article (doi:10.1186/s12948-015-0013-0) contains supplementary material, which is available to authorized users.     

Interleukin-6 potentiates FcεRI-induced PGD2 biosynthesis and induces VEGF from human in situ-matured skin mast cells

Background

Interleukin-6 is a gp130 utilizing cytokine that is consistently associated with allergic diseases like asthma and urticaria in humans where mast cells are known to play a critical role. However, the role of IL-6 in allergic disease in not known. IL-6 was reported to enhance degranulation of in vitro-derived mast cells, but the effect of IL-6 on mediator release from human in situ-matured tissue-isolated mast cells had not been reported.

Acute myocardial infarction system of care in the third world

Background

We studied the characteristics of ST-elevation myocardial infarction (STEMI) patients from a local acute coronary syndrome (ACS) registry in order to find and build an appropriate acute myocardial infarction (AMI) system of care in Jakarta, Indonesia.

Methods

Data were collected from the Jakarta Acute Coronary Syndrome (JAC) registry 2008–2009, which contained 2103 ACS patients, including 654 acute STEMI patients admitted to the National Cardiovascular Center Harapan Kita, Jakarta, Indonesia.

Results

The proportion of patients who did not receive reperfusion therapy was 59% in all STEMI patients and the majority of them (52%) came from inter-hospital referral. The time from onset of infarction to hospital admission was more than 12 h in almost 80% cases and 60% had an anterior wall MI. In-hospital mortality was significantly higher in patients who did not receive reperfusion therapy compared with patients receiving acute reperfusion therapy, either with primary percutaneous coronary intervention (PPCI) or fibrinolytic therapy (13.3% vs 5.3% vs 6.2%, p < 0.001).

Conclusion

The Jakarta Cardiovascular Care Unit Network System was built to improve the care of AMI in Jakarta. This network will harmonise the activities of all hospitals in Jakarta and will provide the best cardiovascular services to the community by giving two reperfusion therapy options (PPCI or pharmaco-invasive strategy) depending on the time needed for the patient to reach the cath-lab.     

Interleukin-8 gene polymorphism is associated with acute coronary syndrome in the Chinese Han population

Background

Acute coronary syndrome (ACS) is one of the most common forms of heart disease. Recent studies have shown that interleukin (IL)-8 plays a key role in the development of atherosclerotic plaques, but the relationship between the common genetic variants of IL-8 and ACS has not been extensively studied.

Methods

This case-control study in the Chinese Han population included 675 patients with ACS and 636 age- and sex-matched controls. We investigated IL-8 polymorphisms and their association with susceptibility to ACS. The investigation was replicated in the second study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay.

Results

IL-8 −251 A/T polymorphism was associated with increased susceptibility to ACS (P = 0.004; odds ratio = 1.30; 95% confidence interval: 1.12–1.53). The second study yielded similar results. An increased IL-8 level was found in the plasma of acute myocardial infarction patients, suggesting that IL-8 −251 A/T may affect the expression of IL-8.

Conclusion

IL-8 −251 A/T polymorphism is associated with ACS risk in the Chinese Han population and the A allele of IL-8 −251 A/T may be an independent predictive factor for ACS.     

Significant alterations of the novel 15 gene signature identified from macrophage-tumor interactions in breast cancer

Background

Tumor microenvironment is composed of a largely altered extracellular matrix with different cell types. The complex interplay between macrophages and tumor cells through several soluble factors and signaling is an important factor in breast cancer progression.

Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet

Objective

To investigate and compare the effects of two common dietary phytosterols, stigmasterol and β-sitosterol, in altering lipid metabolism and attenuating nonalcoholic fatty liver disease (NAFLD).

Nursing role to improve care to infarct patients and patients undergoing heart surgery: 10?years’ experience

Background

The nurse practitioner may be the ideal healthcare worker to create a new environment and may facilitate in the process of expediting discharge and improving patient safety. They can play an intermediary role between the consultants, nurses and patients, thereby combining the aspects of care (nursing) and cure (physicians).

Method

We describe the contribution and role of the nurse practitioner in a teaching hospital and provide an overview of the changes in care and cure that were facilitated by two nurse practitioners in the treatment of cardiac surgery patients or non-complicated acute coronary syndrome patients.

Results

The nurse-led clinic for postoperative patients has registered 1967 patients in the past 10 years. These patients were transferred at a mean of 5.5 days after their bypass operation. All patients had an uneventful clinical course in our hospital and were discharged alive. The period between discharge and outpatient clinic visit could be set at 4 weeks.The post-acute coronary syndrome (ACS) group included 1236 patients. Mortality in this patient cohort was 4% while 0.4% of these patients experienced a re-myocardial infarction. Additional surgery was needed in only 2% of these stable post-infarction patients. The mean length of stay was 5.9 ± 14.5 days.

Conclusion

This observational study confirms that a nurse-led postoperative care unit and post-ACS care unit is feasible and effective for the treatment of patients returning from cardiac surgery or transferred after uncomplicated ACS to a general cardiology ward.     

Chitinase 3-like 1 gene-329G/A polymorphism, plasma concentration and risk of coronary heart disease in a Chinese population

Background

The chitinase-like 1 protein, YKL-40, is involved in inflammation and tissue remodeling. Patients with coronary heart disease (CHD) and acute myocardial infarction have elevated levels of serum YKL-40. The goal of the present study was to investigate whether the chitinase-like 1 gene-329G/A variant (rs10399931) confers susceptibility to CHD, and whether it is associated with the clinical phenotype and severity of disease.

Methods

We performed a case-control study of 410 unrelated CHD patients (coronary stenosis ≥ 50% or documented myocardial infarction) and 442 controls from China. A ligase detection reaction was used to determine a single-nucleotide polymorphism in rs10399931. The genotypic and allelic associations of this single-nucleotide polymorphism with CHD, phenotypes and severity were also evaluated. Plasma levels of YKL-40 were measured using ELISA assays.

Results

Three genotypes, CC, CT, and TT, existed in rs10399931 and there were no significant differences found in either the genotypic or allelic frequencies between the CHD cases and controls. Patients with CHD had higher YKL-40 levels compared to controls and those with acute myocardial infarction had the highest levels of YKL-40 compared to patients with either stable or unstable angina pectoris (all p < 0.01). Rs10399931 affected neither the main anthropometric or metabolic characteristics, nor did there exists any association between rs10399931 and the severity of coronary lesions assessed by Gensini scores (all p > 0.05).

Conclusions

Our results do not support that rs10399931 is associated with clinical phenotypes of CHD and the extent of coronary lesions; however, YKL-40 levels are higher in CHD patients and associated with its clinical phenotypes.     

Effect of different training mode on Interleukin-6 (IL-6) and C-reactive protein (CRP) in type 2 diabetes mellitus (T2DM) patients

[Purpose]

This study was carried out to investigate the effects of different training modes on IL-6 and CRP in patients with type 2 diabetes mellitus (T2DM).

[Methods]

The subjects consisted of 16 middle-aged women with type 2 diabetes mellitus (T2DM), all of whom had no other complications. The 16 subjects were randomly assigned to two experimental groups: the circuit training group (CTG, n = 8) and aerobic training group (ATG, n = 8). Based on measured THR (target heart rate) for maximum oxygen consumption rate, the circuit training group (CTG) exercised at 60% intensity, 60 min/day, 5 sets, 3 days/week for 12 weeks. Based on measured THR (target heart rate) for maximum oxygen consumption rate, the aerobic training group (ATG) exercised at 60% intensity (which was increased gradually in weeks 4, 7, and 10) 60 min/day, 3 days/week for 12 weeks.

[Results]

The results are as follows. Significant decreases in the post training values of weight, % Fat, BMI, IL-6 and CRP (p < .05) were observed in the CTG compared to pre-training. However, there were no differences in the physical characteristic and blood inflammatory factors between the groups (ATG & CTG).

[Conclusion]

In conclusion, the results of this study suggest that circuit training (CT) may be considered as an effective training mode for helping to decrease the blood inflammatory factors (IL-6 and CRP) in patients with type 2 diabetes mellitus (T2DM).     

Adoption of prasugrel into routine practice: rationale and design of the Rijnmond Collective Cardiology Research (CCR) study in percutaneous coronary intervention for acute coronary syndromes

Background

Platelet inhibition is crucial in reducing both short- and long-term atherothrombotic risks in patients with acute coronary syndromes (ACS) managed with percutaneous coronary intervention (PCI). Based on randomised trials, recent recommendations in the current guidelines include the endorsement of prasugrel as a first-choice adenosine diphosphate receptor inhibitor. Yet, there is limited experience with the use of prasugrel in routine practice.

Methods

The Rijnmond Collective Cardiology Research (CCR) registry is a prospective, observational study that will follow-up 4000 PCI-treated ACS patients in the larger region of Rotterdam, the Netherlands. Based on recently implemented hospital protocols, all patients will receive prasugrel as first-choice antiplatelet agent, unless contraindicated, in accordance with European guidelines, and will be followed for up to 1 year post-discharge for longitudinal assessment of outcomes and bleeding events. This registry exemplifies a collaborative study design that employs a regional PCI registry platform and provides feedback to participating sites regarding their practice patterns, thereby supporting and promoting improvement of quality of care.

Conclusion

The CCR registry will evaluate the adoption of prasugrel into routine clinical practice and thus, will provide important evidence with regard to the benefits and risks of real-world utilisation of prasugrel as antiplatelet therapy in PCI-treated ACS patients.     

Platelet Turnover in Stable Coronary Artery Disease – Influence of Thrombopoietin and Low-Grade Inflammation

Background

Newly formed platelets are associated with increased aggregation and adverse outcomes in patients with coronary artery disease (CAD). The mechanisms involved in the regulation of platelet turnover in patients with CAD are largely unknown.

Aim

To investigate associations between platelet turnover parameters, thrombopoietin and markers of low-grade inflammation in patients with stable CAD. Furthermore, to explore the relationship between platelet turnover parameters and type 2 diabetes, prior myocardial infarction, smoking, age, gender and renal insufficiency.

Methods

We studied 581 stable CAD patients. Platelet turnover parameters (immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell-ratio) were determined using automated flow cytometry (Sysmex XE-2100). Furthermore, we measured thrombopoietin and evaluated low-grade inflammation by measurement of high-sensitive CRP and interleukin-6.

Results

We found strong associations between the immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell ratio (r = 0.61–0.99, p<0.0001). Thrombopoietin levels were inversely related to all of the platelet turnover parameters (r = −0.17–−0.25, p<0.0001). Moreover, thrombopoietin levels were significantly increased in patients with diabetes (p = 0.03) and in smokers (p = 0.003). Low-grade inflammation evaluated by high-sensitive CRP correlated significantly, yet weakly, with immature platelet count (r = 0.10, p = 0.03) and thrombopoietin (r = 0.16, p<0.001). Also interleukin-6 correlated with thrombopoietin (r = 0.10, p = 0.02).

Conclusion

In stable CAD patients, thrombopoietin was inversely associated with platelet turnover parameters. Furthermore, thrombopoietin levels were increased in patients with diabetes and in smokers. However, low-grade inflammation did not seem to have a substantial impact on platelet turnover parameters.     

Chemokine CC-motif ligand 2 participates in platelet function and arterial thrombosis by regulating PKCα-P38MAPK-HSP27 pathway

Background

Studies indicate that chemokine CC-motif ligand 2 (CCL2) is involved in inflammation and atherosclerosis. However, the roles and mechanisms of CCL2 on platelet function and arterial thrombosis are unknown.

Prognostic value of rising mean platelet volume during hospitalization in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Background

The prognostic significance of changes in mean platelet volume (MPV) during hospitalization in ST segment elevation myocardial infarction (STEMI) patients underwent primary percutaneous coronary intervention (pPCI) has not been previously evaluated. The aim of this study was to determine the association of in-hospital changes in MPV and mortality in these patients.

Methods

Four hundred eighty consecutive STEMI patients were enrolled in this retrospective study. The patients were grouped as survivors (n?=?370) or non-survivors (n?=?110). MPV at admission, and at 48–72?h was evaluated. Change in MPV (MPV at 48–72?h minus MPV on admission) was defined as ΔMPV.

Results

At follow-up, long-term mortality was 23%. The non-survivors had a high ΔMPV than survivors (0.37 (??0.1–0.89) vs 0.79 (0.30–1.40) fL, p?<? 0.001). A high ΔMPV was an independent predictor of all cause mortality ((HR: 1.301 [1.070–1.582], p?=?0.008). Morever, for long-term mortality, the AUC of a multivariable model that included age, LVEF, Killip class, and history of stroke/TIA was 0.781 (95% CI:0.731–0.832, p?<? 0.001). When ΔMPV was added to a multivariable model, the AUC was 0.800 (95% CI: 0.750–0.848, z?=?2.256, difference p?=?0.0241, Fig. 1). Also, the addition of ΔMPV to a multivariable model was associated with a significant net reclassification improvement estimated at 24.5% (p?=?0.027) and an integrated discrimination improvement of 0.014 (p?=?0.0198).

Conclusions

Rising MPV during hospitalization in STEMI patients treated with pPCI was associated with long-term mortality.

     

Human αS1-casein induces IL-8 secretion by binding to the ecto-domain of the TLR4/MD2 receptor complex

Background

The milk protein α_S1-casein was recently reported to induce secretion of proinflammatory cytokines via Toll-like receptor 4 (TLR4). In this study, α_S1-casein was identified as binder of theTLR4 ecto domain.

Smoking cessation after an acute coronary syndrome: immediate quitters are successful quitters

Background

Cardiovascular disease (CVD) prevention guidelines stress the importance of smoking cessation and recommend intensive follow-up. To guide the development of such cessation support strategies, we analysed the characteristics that are associated with successful smoking cessation after an acute coronary syndrome (ACS).

Methods

We used data from the Randomised Evaluation of Secondary Prevention for ACS patients coordinated by Outpatient Nurse SpEcialists (RESPONSE) trial (n = 754). This was designed to quantify the impact of a nurse-coordinated prevention program, focusing on healthy lifestyles, traditional CVD risk factors and medication adherence. For the current analysis we included all smokers (324/754, 43 %). Successful quitters were defined as those who reported abstinence at 1 year of follow-up.

Results

The majority of successful quitters quit immediately after the ACS event and remained abstinent through 1 year of follow-up, without extra support (128/156, 82 %). Higher education level (33 vs. 15 %, p < 0.01), no history of CVD (87 vs. 74 %, p < 0.01) and being on target for LDL-cholesterol level at 1 year (78 vs. 63 %, p < 0.01) were associated with successful quitting.

Conclusion

The majority of successful quitters at 1 year stopped immediately after their ACS. Patients in this group showed that it was within their own ability to quit, and they did not relapse through 1 year of follow-up. Our study indicates that in a large group of patients who quit immediately after a life-threatening event, no relapse prevention program is needed.     

The inflammasome pathway is amplified and perpetuated in an autocrine manner through connexin43 hemichannel mediated ATP release

Background

Connexin43 hemichannels have been implicated in many inflammatory diseases including diabetic retinopathy (DR). Particularly, hemichannel-mediated ATP release has been associated with inflammasome pathway activation. Using an in vitro cell culture model, we evaluated hemichannel roles in response to inflammatory cytokines under high glucose (HG) conditions and propose a mechanism by which a connexin43 hemichannel-mediated autocrine ATP feedback loop augments chronic inflammatory disease.

Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP – Results from the German competence network CAPNETZ

Background

Aim of this study was to evaluate the correlation of inflammatory markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC) with microbiological etiology of CAP.

Methods

We enrolled 1337 patients (62 ± 18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were classified according to microbial diagnosis and CRB-65 score.

Results

In patients with typical bacterial CAP, levels of PCT, CRP and WBC were significantly higher compared to CAP of atypical or viral etiology. There were no significant differences in PCT, CRP and WBC in patients with atypical or viral etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI 0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65, PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison to outpatients.

Conclusion

PCT, CRP and WBC are highest in typical bacterial etiology in CAP but do not allow individual prediction of etiology. In contrast to CRP and WBC, PCT is useful in severity assessment of CAP.