Histopathological Features of Aspirated Thrombi after Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction

BACKGROUND: Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population. METHODOLOGY/PRINCIPAL FINDINGS: Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (<1 day), lytic (1-5 days), or organized (>5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus. CONCLUSIONS/SIGNIFICANCE: Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients

Granulocytes in coronary thrombus evolution after myocardial infarction--time-dependent changes in expression of matrix metalloproteinases

Remodeling of extracellular matrix is a key process during wound healing, which is strictly regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors [tissue inhibitors of metalloproteinases (TIMPs)]. In this study, we evaluated intrathrombotic MMPs and TIMPs and their cellular origin during thrombus evolution after disruption of coronary atherosclerotic plaque. Thrombectomy materials (N=120) obtained from patients with acute myocardial infarction were histologically classified in three groups based on thrombus age: fresh ( 5days) thrombi; materials showing a heterogeneous composition were classified according to oldest part. Presence and cellular origin of MMPs (MMP-1, MMP-2, MMP-8, MMP-9, and MMP-14) and TIMPs (TIMP-1, TIMP-2, and TIMP-3) was evaluated with immunostains (double) and with polymerase chain reaction. MMPs and TIMPs were present in all the thrombectomy samples. A distinct temporal change in extent and cellular origin of MMPs and TIMPs during thrombus evolution was observed. In the early (fresh and lytic) stages of thrombus, high numbers of neutrophilic granulocytes occupy the thrombus mass and produce large amounts of MMPs and TIMPs. However, with progression of thrombus evolution (organizing stage) and diminishment of neutrophil granulocytes, there is disappearance of MMP-8 and MMP-9, steep decline of MMP-1 and TIMP-2, and progressive decrease of TIMP-3. In contrast, intrathrombotic MMP-2 and MMP-14 are present at a constant high level during the entire process of thrombus evolution. These temporal changes indicate a complex time-dependent function of MMPs, which are largely granulocyte derived, in the healing process of thrombus after plaque disruptio

Microvascular endoglin (CD105) expression correlates with tissue markers for atherosclerotic plaque vulnerability in an ageing population with multivessel coronary artery disease

Li X, van der Meer J J, van der Loos C M, Ploegmakers H J P, de Boer O J, de Winter R J & van der Wal A C ?(2012) Histopathology similar to 61, 8897 Microvascular endoglin (CD105) expression correlates with tissue markers for atherosclerotic plaque vulnerability in an ageing population with multivessel coronary artery disease Aims: Vulnerable atherosclerotic plaques are lesions with a high propensity to develop plaque disruption and superimposed thrombosis. No systematic studies have been carried out on tissue markers for plaque vulnerability throughout the entire coronary artery system at the end stages of coronary atherosclerosis. Methods and results: Nine autopsied patients (mean age 77 years) with angiographically severe trivascular coronary atherosclerosis were selected for this study. All visible lesions in postmortem coronary angiograms (n = 125) were histologically and immunohistochemically screened for the presence of intraplaque haemorrhages (activated) microvessels and inflammatory infiltrates. Intraplaque haemorrhages were observed in 76/125 plaques (61%). Chronic inflammation was found superficially in 59/125 plaques (47%) and deeply inside the plaque tissue in 103/125 plaques (83%). Microvessels were found in 100/125 lesions (80%), of which 58% showed endothelial expression of the vascular activation marker CD105. Moreover, microvascular CD105 positivity correlated positively with plaque haemorrhage and deeply seated plaque inflammation. Conclusions: Plaque inflammation and haemorrhages can be found at a high frequency throughout the coronary artery system of elderly patients with multivessel coronary atherosclerosis. Microvascular expression of endoglin (CD105), which correlates positively with both of these features of plaque vulnerability, can serve as a marker of the risk of developing coronary thrombotic complication

Neutrophils, neutrophil extracellular traps and interleukin-17 associate with the organisation of thrombi in acute myocardial infarction

Neutrophils are important cellular sources of interleukin (IL) 17A and -F. Moreover, upon activation neutrophils are able to excrete chromatin embedded with components from their cytoplasmic granules to form 'neutrophil extracellular traps' (NETs). Recent studies suggested that NETs contribute to thrombosis by promoting fibrin deposition and platelet aggregation. IL17A may also promote thrombosis by enhancing platelet aggregation. In the present study we investigated the presence of neutrophils, NETs and IL17A and -F in coronary thrombosuction specimens obtained from patients after acute myocardial infarction. Neutrophils and NETs were identified using histochemical (HE, Feulgen procedure) and immunohistochemical stainings (Histone H1, myeloperoxidase, neutrophil elastase) in 15 fresh, 15 lytic and 15 organised thrombi. The presence and distribution of IL17A and -F was studied using (immuno)histochemical double staining and spectral image analysis, rtPCR and Western blot. High numbers of neutrophils are present (10-30% of the thrombus mass) in fresh and lytic, but not in organized thrombus. NETs were frequently observed in fresh (4/15) and lytic (12/15), but never in organised thrombus specimens. Double staining combining the Feulgen reaction with Histone-H1, MPO or neutrophil elastase confirmed colocalisation with DNA. Cytoplasmatic IL17A/F staining was found in the majority of the neutrophils, extracellularly and in NETs. Western blotting confirmed the presence of IL17A and IL17F in thrombus specimens. In conclusion, a large burden of neutrophils, neutrophil extracellular traps and IL17A and -F are important constituents of fresh and lytic thrombus after acute myocardial infarction. The specific colocalisation of these indicates a role during thrombus stabilisation and growt

Prevalence, risk factors, and optimal way to determine overweight, obesity, and morbid obesity in the first Dutch cohort of 2338 long-term survivors of childhood cancer:a DCCSS-LATER study

Background: Overweight and obesity are common challenges among childhood cancer survivors. Overweight may be disguised, as survivors can have normal weight but high fat percentage (fat%) on dual-energy X-ray absorptiometry (DXA). We aimed to assess prevalence, identify determinants and biomarkers, and assess which method captures overweight best, in a nationwide cohort. Methods: The prevalence of overweight and obesity, primarily defined by body mass index (BMI), was assessed in the DCCSS-LATER cohort of adult survivors treated from 1963-2002, with the LifeLines cohort as reference. The associations between risk factors and overweight metrics were investigated using logistic regression. Additional overweight metrics included DXA fat%, waist circumference (WC), waist/hip ratio (WHR), waist/height ratio (WHtR), and high-molecular-weight (HMW) adiponectin. Results: A total of 2338 (mean age 35.5 years, follow-up 28.3 years) survivors participated. The overweight prevalence was 46.3% in men and 44.3% in women (obesity 11.2% and 15.9%, morbid obesity 2.4% and 5.4%), with highest rates among brain tumor survivors. Compared to controls, there was no overall increased overweight rate, but this was higher in women &gt; 50 years, morbid obesity in men &gt; 50 years. Overweight at cancer diagnosis (adjusted odds ratio [aOR] = 3.83, 95% CI 2.19-6.69), cranial radiotherapy (aOR = 3.21, 95% CI 1.99-5.18), and growth hormone deficiency (separate model, aOR = 1.61, 95% CI 1.00-2.59) were associated with overweight. Using BMI, WC, WHR, and WHtR, overweight prevalence was similar. Low HMW adiponectin, present in only 4.5% of survivors, was an insensitive overweight marker. Dual-energy X-ray absorptiometry–based classification identified overweight in an additional 30%, particularly after abdominal radiotherapy, total body irradiation, anthracyclines, and platinum. Conclusions: Overweight occurs in almost half of long-term survivors. There was no overall increased incidence of overweight compared to controls. We identified factors associated with overweight, as well as subgroups of survivors in whom DXA can more reliably assess overweight.</p