CXCR4 positive and angiogenic monocytes in myocardial infarction

2013 ◽  
Vol 109 (02) ◽  
pp. 255-262 ◽  
Author(s):  
Benjamin Wrigley ◽  
Silvia Montoro-Garcia ◽  
Gregory Lip ◽  
Eduard Shantsila ◽  
Luke Tapp

SummaryLimited data are available on the role of monocytes in cardiac repair. In the present study, we evaluated the dynamic alterations of monocytes with reparative and angiogenic potential in patients with myocardial infarction(MI). Reparative CXCR4+ monocytes, and CD34+ and KDR+ monocytes with angiogenic potential derived from individual monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (n=50) and stable coronary artery disease (CAD, n=40). Parameters were measured on days 1, 3, 7 and 30 post MI. Monocyte subsets were defined as CD14++CD16–CCR2+ (‘classical’, Mon1), CD14++CD16+CCR2+ (‘intermediate’, Mon2), CD14+CD16++CCR2– (‘non-classical’, Mon3). Plasma levels of inflammatory cytokines, fibrinolytic factors and microparticles (MPs) were assessed on day 1. CXCR4+ and KDR+ monocytes were increased following MI, being more prominently associated with Mon2 (median[IQR] of CXCR4+ Mon2 60[25–126] per μl in STEMI vs. 27[21–41] per μl in stable CAD). The counts of CXCR4+ Mon2 in STEMI significantly reduced by day 30 of follow-up (27[18–47], p<0.001). Expression of the pro-reparative scavenger receptor CD163 on Mon3 was reduced in acute MI (p=0.008), and on other subsets later during the follow-up with lowest levels at day 3 post-MI (p<0.001 for Mon1, p=0.02 for Mon2). CD204 expression on Mon1 correlated with tissue type plasminogen activator levels (r=0.46, p=0.001). Interleukin(IL)6 levels correlated with counts of Mon2-derived CXCR4+ and KDR+ cells. Interleukin-1β correlated with KDR+ Mon2 counts. IL10 correlated with CXCR4+ Mon2 levels. Low count of CXCR4+ Mon2 and low CD163 expression by Mon2 were associated with higher ejection fraction six-weeks after MI. In conclusion, the Mon2 subset has the most prominent role in the observed changes in reparative monocytes in MI. The association of reparative monocytes with inflammatory/fibrinolytic markers indicates a complex interplay of these cells in the post-MI state.Note: The review process for this paper was fully handled by Prof. Christian Weber, Editor in Chief.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Darmon ◽  
G Ducrocq ◽  
Y Elbez ◽  
E Sorbets ◽  
R Ferrari ◽  
...  

Abstract Background The prevalence, and prognostic implication of left bundle branch block (LBBB) in general population and patients admitted for acute myocardial infarction (MI) as been extensively studied. However, data are scarce about patients with stable coronary artery disease (CAD) and it remains unclear whether LBBB is only a marker of a severe cardiomyopathy or an independent predictor of events in these patients. Purpose We aimed to describe the prevalence, incidence and prognostic implications of LBBB in patients with stable CAD. Additionally, we aimed to describe the incidence of newly diagnosed LBBB that occurred without recent myocardial infarction. Methods CLARIFY is an international registry of more than 30.000 patients with stable CAD. LBBB was collected at baseline and at each follow-up visit, and patients were considered to have LBBB if the length of the QRS complex was of more than 120 milliseconds. Patients with previous pacemaker implantation of internal cardiac defibrillator were excluded. The primary outcome was a composite of cardiovascular (CV) Death, MI or stroke, and secondary outcomes included hospitalization for heart failure (HF) or the need for pacemaker implantation. Results From the 23.457 patients with available data regarding LBBB status, 1.041 (4.4%) had LBBB at baseline and 1.237 (5.3%) had at least one LBBB assessed during 5-year follow-up. Only 21 patients with newly diagnosed LBBB overtime, had a documented MI the same year. Compared to patients without LBBB, patients with LBBB had a higher risk profile regarding age (67.2±10.1 versus 63.6±10.4 years, p<0.0001), history of coronary artery bypass grafting (29.2% vs 23.7%, p<0.0001), diabetes (35.1% vs 28.4%, p<0.0001), and HF (25.2% vs 16.8%, p<0.0001) (Table). In unadjusted analysis, patients with LBBB had a higher risk of primary outcome (13.4% vs 8.7%, p<0.0001) and each secondary outcome. In multivariate analysis taking into account several possible confounders, there was no difference in the rate of CV death, MI or stroke between LBBB or no-LBBB patients (adjusted HR 1.04, 95% CI 0.85–1.29). However, patients with LBBB had a higher rate of pacemaker implantation (adjusted HR 2.21, 95% CI 1.55–3.15, p<0.0001) and hospitalization for HF (adjusted HR 1.53, 95% CI 1.25–1.88, p<0.0001) (Figure). Outcomes according to LBBB status Conclusion The prevalence of LBBB in patients with stable CAD was 4.4% and 5.3% with 5-year follow-up. The overwhelming majority of newly diagnosed LBBB were not contemporary of documented myocardial infarction. LBBB was not associated with a higher rate of major adverse cardiovascular events, including all cause mortality but with a higher risk of pacemaker implantation and hospitalization for heart failure. To our knowledge this is the first study reporting such results in a broad population of stable CAD patients. Acknowledgement/Funding None


Author(s):  
Tomonori Itoh ◽  
◽  
Hiromasa Otake ◽  
Takumi Kimura ◽  
Yoshiro Tsukiyama ◽  
...  

AbstractThe purpose of this study was to assess early and late vascular healing in response to bioresorbable-polymer sirolimus-eluting stents (BP-SESs) for the treatment of patients with ST-elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). A total of 106 patients with STEMI and 101 patients with stable-CAD were enrolled. Optical frequency-domain images were acquired at baseline, at 1- or 3-month follow-up, and at 12-month follow-up. In the STEMI and CAD cohorts, the percentage of uncovered struts (%US) was significantly and remarkably decreased during early two points and at 12-month (the STEMI cohort: 1-month: 18.75 ± 0.78%, 3-month: 10.19 ± 0.77%, 12-month: 1.80 ± 0.72%; p < 0.001, the CAD cohort: 1-month: 9.44 ± 0.78%, 3-month: 7.78 ± 0.78%, 12-month: 1.07 ± 0.73%; p < 0.001 respectively). The average peri-strut low-intensity area (PLIA) score in the STEMI cohort was significantly decreased during follow-up period (1.90 ± 1.14, 1.18 ± 1.25, and 1.01 ± 0.72; p ≤ 0.001), whereas the one in the CAD cohort was not significantly changed (0.89 ± 1.24, 0.67 ± 1.07, and 0.64 ± 0.72; p = 0.59). In comparison with both groups, differences of %US and PLIA score at early two points were almost disappeared or close at 12 months. The strut-coverage and healing processes in the early phase after BP-SES implantation were significantly improved in both cohorts, especially markedly in STEMI patients. At 1 year, qualitatively and quantitatively consistent neointimal coverage was achieved in both pathogenetic groups.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hack-Lyoung Kim ◽  
Jung Pyo Lee ◽  
Nathan Wong ◽  
Woo-Hyun Lim ◽  
Jae-Bin Seo ◽  
...  

AbstractThe role of ST2 in stable coronary artery disease (CAD) has not yet been well defined. This study was performed to investigate baseline serum soluble ST2 (sST2) level can predict clinical outcomes in patients with stable CAD. A total of 388 consecutive patients with suspected CAD (65 years and 63.7% male) in stable condition referred for elective invasive coronary angiography (ICA) was prospectively recruited. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke during clinical follow-up was assessed. Most of the patients (88.0%) had significant CAD (stenosis ≥ 50%). During median follow-up of 834 days, there was 29 case of MACE (7.5%). The serum sST2 level was significantly higher in patients with MACE than those without (47.3 versus 30.6 ng/ml, P < 0.001). In multiple Cox regression model, higher sST2 level (≥ 26.8 ng/ml) was an independent predictor of MACE even after controlling potential confounders (hazard ratio, 13.7; 95% confidence interval 1.80–104.60; P = 0.011). The elevated level of baseline sST2 is associated with an increased risk of adverse clinical events in stable CAD patients. Studies with larger sample size are needed to confirm our findings.


2013 ◽  
Vol 110 (08) ◽  
pp. 340-348 ◽  
Author(s):  
Benjami Wrigley ◽  
Silvia Montoro-Garcia ◽  
Eduard Shantsila ◽  
Luke Tapp ◽  
Gregory Lip

SummaryThe role of individual monocyte subsets in inflammation and recovery post-myocardial infarction (MI) is insufficiently understood. It was the objective of this study to evaluate the dynamics of monocyte expression of receptors to vascular cell adhesion molecule (VCAM-1r), intercellular adhesion molecule (ICAM-1r), and interleukin-6 (IL-6r) following MI and their relation to inflammatory cytokines, fibrinolytic factors and annexin V-binding microparticles. Expression of VCAM-1r, ICAM-1r, IL-6r on CD14++CD16–(Mon1), CD14++CD16+(Mon2), CD14+CD16++(Mon3) monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (STEMI, n=50), non-STEMI (n=48) and stable coronary artery disease (n=40). In STEMI, parameters were measured on days 1, 3, 7, 30. On admission with STEMI, VCAM-1r expression was reduced on Mon1 (p=0.007), Mon2 (p=0.036), Mon3 (p=0.005), whilst in NSTEMI there was significant up-regulation of expression by Mon2 (p=0.024) and Mon3 (p=0.049). VCAM-1r on Mon1 correlated positively with plasma IL-1β levels (p=0.001). IL-6r was reduced on Mon2 in acute STEMI, with upregulation of the receptor on Mon1 and Mon2 during follow-up. IL-6r density correlated negatively with plasma levels of tissue-type plasminogen activator (p=0.0005 for Mon1, p=0.001 for Mon2 and Mon3), and positively with annexin V-binding microparticles (p=0.03 for Mon1, p=0.005 for Mon2 and p=0.005 for Mon3). There was no change in monocyte ICAM-1r expression. In conclusion, expression of IL-6r and VCAM-1r is reduced on circulating monocyte subsets involved in inflammatory responses in STEMI. This may represent a regulatory feed-back mechanism aiming to re-balance the marked inflammation which is typically present following acute MI or selective homing of monocytes with high receptor expression to damaged myocardium.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.


2016 ◽  
Vol 39 (3) ◽  
pp. 79 ◽  
Author(s):  
Mehmet N Akkus ◽  
Adil Ormam ◽  
Sabri Seyis ◽  
Çagdas Baran ◽  
Aysegül Görür ◽  
...  

Purpose: The purpose of this study was to determine whether the plasma levels of soluble extracellular matrix metalloproteinase inducer (EMMPRIN) differed among the patients with ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and stable coronary artery disease (CAD) and the healthy controls, and to identify the factors associated with the differences in plasma levels of this this protein among patients in these groups. Methods: Plasma EMMPRIN levels were compared among four age- and sex-matched groups of patients with STEMI, NSTEMI and stable CAD and healthy controls (n=44 per group), then logistic regression and correlation analyses were conducted for the whole acute myocardial infarction (AMI) patients group. Results: EMMPRIN levels were significantly higher in the STEMI (39.4±9.2ng/mL) and NSTEMI (37.1±10.5ng/mL) groups than in either the stable CAD (27.5±4.7ng/mL) or control (24.5±5.8ng/mL) groups (p


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Konstantinos Mourouzis ◽  
Gerasimos Siasos ◽  
Evangelos Oikonomou ◽  
Marina Zaromitidou ◽  
Vicky Tsigkou ◽  
...  

Abstract Background Lipoprotein-associated Phospholipase A2 (Lp-PLA2), can exert proinflammatory as well as proatherogenic properties on the vascular wall. The current study sought to evaluate the influence of high Lp-PLA2 levels on indices of arterial wall properties in patients with stable coronary artery disease (CAD). Methods Three hundred seventy-four consecutive patients with stable CAD (mean age 61 ± 11 years, 89% males) were enrolled in this single-center cross-sectional study. Flow-mediated dilation (FMD) was used to assess endothelial function and augmentation index (AIx) of the central aortic pressure was used to assess reflected waves. ELISA was used to determine Lp-PLA2 serum levels. Results After dividing the participants in 3 equal groups based on the tertiles of circulating Lp-PLA2 values, no significant differences were demonstrated between those in the 3rd tertile with Lp-PLA2 values > 138 μg/L, in the 2nd tertile with Lp-PLA2 values between 101 and 138 μg/L and in the 1st tertile (Lp-PLA2 values < 101 μg/L) regarding age, male gender, smoking habits, family history of CAD or history of a previous myocardial infarction, diabetes mellitus, arterial hypertension, hyperlipidemia, duration of CAD and treatment with relevant medication. Importantly, subjects with Lp-PLA2 values in the highest tertile, had significantly reduced FMD values compared to the middle and lower tertile (4.43 ± 2.37% vs. 4.61 ± 1.97% vs. 5.20 ± 2.52% respectively, P = 0.03). Patients in the highest tertile of Lp-PLA2 values had significantly higher AIx values (24.65 ± 8.69% vs. 23.33 ± 9.65%, P = 0.03), in comparison to the lowest tertile, with Lp-PLA2 values < 101 μg/L. A linear regression analysis showed that Lp-PLA2 values > 138 μg/L negatively correlated to FMD [b = − 0.45 (95% CI: − 0.79 – -0.11), P = 0.01] and AIx values [b = 1.81 (95% CI: 0.57–3.05), P < 0.001] independently of cofounders like gender, age, diabetes mellitus, arterial hypertension, dyslipidemia, smoking habits, family history of CAD, history of previous myocardial infarction, serum glucose, circulating lipid levels, duration of CAD, antihypertensive medication, antidiabetic drugs, statin therapy and treatment with β-blockers. Conclusions Elevated Lp-PLA2 levels relate to endothelial dysfunction and arterial stiffness in patients with stable CAD independently from classical risk factors for CAD, statin use, antihypertensive treatment, and duration of the disease.


2018 ◽  
Vol 47 (04) ◽  
pp. 778-790 ◽  
Author(s):  
Gard Svingen ◽  
Eva Pedersen ◽  
Reinhard Seifert ◽  
Jan Kvaløy ◽  
Øivind Midttun ◽  
...  

AbstractSystemic fibrinogen and neopterin are related to inflammation. We investigated the prognostic utility and possible interactions of these biomarkers in stable coronary artery disease (SCAD) patients undergoing coronary angiography. We included 3,545 patients with suspected stable angina with a median follow-up of 7.3 and 10.2 years for incident acute myocardial infarction (AMI) and all-cause mortality, respectively. Prospective associations were explored by Cox regression. Potential effect modifications were investigated according to strata of fibrinogen, neopterin or high-sensitivity troponin T (hsTnT) below and above the median, as well as gender and smoking habits. During follow-up, 543 patients experienced an AMI and 769 patients died. In a multivariable model, the hazard ratios (HRs; 95% confidence interval [CI]) per 1 SD increase for fibrinogen in relation to these endpoints were 1.30 (1.20, 1.42; p < 0.001) and 1.22 (1.13, 1.31; p < 0.001), respectively. For neopterin, the HRs (95% CI) were 1.31 (1.23, 1.40; p < 0.001) and 1.24 (1.15, 1.34; p < 0.001), respectively. No significant interaction between fibrinogen and neopterin was observed. The prognostic utility of neopterin for incident AMI was improved in patients with an hsTnT above the median, for total mortality in non-smokers, and for both total mortality and AMI in females. In conclusion, both fibrinogen and neopterin were associated with future AMI and total mortality, but had low discriminatory impact. No interaction was observed between these two biomarkers. The prognostic utility of neopterin was improved in patients with hsTnT levels above the median, and in females and non-smokers.


2020 ◽  
Vol 75 (1) ◽  
pp. 46-53
Author(s):  
Nalalya Yu. Sokolova ◽  
Elena Z. Golukhova

Background: The main methods of treating patients with stable coronary artery disease (CAD) are myocardial revascularization with coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI). These are two fundamentally different in technique and volume of surgical interventions; PCI is associated with rapid rehabilitation of the patient, and only CABG demonstrated effective in survival benefit. Aims: Comparison of the long-term results of myocardial revascularization with CABG and PCI in patients with stable CAD. Methods: The results of a prospective one-center cohort study of 369 patients with stable CAD are presented, the average age is 60.1 5.4 years. Patients were randomized into 2 groups by the Heart Team: CABG (n = 196) and PCI (n = 173). In each group, subgroups were identified depending on the severity of the coronary lesion, and the CABG group was also separately studied in according to CABG technique ― beating-heart (off-pump) and with cardiopulmonary bypass (on-pump). The average follow-up was 54.3 7 months. The main outcomes of the study were major adverse cardiac and cerebral events (MACCE): death from all causes, cardiac mortality, nonfatal myocardial infarction (MI), nonfatal stroke and repeated coronary revascularization. Results: Over the 5-year follow-up period, no differences were found between the CABG and PCI groups with a low complexity of coronary artery lesions (SYNTAX Score 14.2 4.8) in terms of survival, cardiac mortality, nonfatal MI and stroke, and the need for repeated myocardial revascularization. Patients with stenosis of the left main coronary artery (LMCA) and/or multivascular CA disease (SYNTAX Score 25.8 5.0) in the long-term follow-up after CABG and PCI did not differ in MACCE, but the CABG group demonstrated a significant advantage in repeated myocardial revascularization. No significant differences were found in any study endpoint in patients after CABG on-pump versus off-pump. Conclusions: Our study demonstrates the advantage of CABG in patients with stable CAD with stenosis of the LMCA and/or multivascular CA disease, and which CABG technique should depends on the comorbidity of the patient, the experience of the surgeon and the surgical center.


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