Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014
In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation.... more In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the presence of activated macrophages in human atherosclerotic plaques by (99m)Tc-folate imaging and to evaluate whether this technique can discriminate between an M1-like and M2-like macrophage phenotype. Carotid endarterectomy specimens of 20 patients were incubated with (99m)Tc-folate, imaged using micro-SPECT, and divided into 3-mm slices. The mean accumulation was calculated per slice, and the distribution of M1-like and M2-like macrophages per slice was quantified by immunohistochemical staining for CD86 as well as inducible nitric oxide synthase (iNOS) for M1 and CD163 and FR-β for M2 macrophages. Monocytes from healthy donors were differentiated toward M1-like or M2-like phenotype by in vitro cultu...
Therapy advice based on dual-source computed tomography (DSCT) in comparison with coronary angiog... more Therapy advice based on dual-source computed tomography (DSCT) in comparison with coronary angiography (CAG) was investigated and the results evaluated after 1-year follow-up. Thirty-three consecutive patients (mean age 61.9 years) underwent DSCT and CAG and were evaluated independently. In an expert reading (the "gold standard"), CAG and DSCT examinations were evaluated simultaneously by an experienced radiologist and cardiologist. Based on the presence of significant stenosis and current guidelines, therapy advice was given by all readers blinded from the results of other readings and clinical information. Patients were treated based on a multidisciplinary team evaluation including all clinical information. In comparison with the gold standard, CAG had a higher specificity (91%) and positive predictive value (PPV) (95%) compared with DSCT (82% and 91%, respectively). DSCT had a higher sensitivity (96%) and negative predictive value (NPV) (89%) compared with CAG (91% and 83%, respectively). The DSCT-based therapy advice did not lead to any patient being denied the revascularization they needed according to the multidisciplinary team evaluation. During follow-up, two patients needed additional revascularization. The high NPV for DSCT for revascularization assessment indicates that DSCT could be safely used to select patients benefiting from medical therapy only.
Early detection of myocardial ischemia is of major importance in critical-care medicine. Changes ... more Early detection of myocardial ischemia is of major importance in critical-care medicine. Changes of lactate or glucose levels in the cardial venous efflux may be useful parameters. We succeeded in integrating an ultrafiltration membrane in a cardiac catheter for continuous sampling. The ultrafiltrate was analyzed outside the body, resulting in a lag-time of about 24 min. Biosensors in a flow-injection
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014
In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation.... more In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the presence of activated macrophages in human atherosclerotic plaques by (99m)Tc-folate imaging and to evaluate whether this technique can discriminate between an M1-like and M2-like macrophage phenotype. Carotid endarterectomy specimens of 20 patients were incubated with (99m)Tc-folate, imaged using micro-SPECT, and divided into 3-mm slices. The mean accumulation was calculated per slice, and the distribution of M1-like and M2-like macrophages per slice was quantified by immunohistochemical staining for CD86 as well as inducible nitric oxide synthase (iNOS) for M1 and CD163 and FR-β for M2 macrophages. Monocytes from healthy donors were differentiated toward M1-like or M2-like phenotype by in vitro cultu...
Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, 2009
Background. In idiopathic dilated cardiomyopathy (IDC) an imbalance between myocardial oxygen con... more Background. In idiopathic dilated cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. Subclinical myocardial ischaemia may contribute to progressive deterioration of left ventricular function. The relation between regional myocardial perfusion reserve (MPR) and contractile performance was investigated.Methods. Patients with newly diagnosed IDC underwent positron emission tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dypiridamole stress), and (18)F-fluorodeoxyglucose viability tracer and a dobutamine stress MRI. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17-segment model.Results. Twenty-two patients were included (age 49+/-11 years; 15 males, LVEF 33+/-10%). With MRI, a total of 305 segments could be analysed. Wall motion abnormalities at rest were present in 127 (35.5%) segments and in 103 (29.9%) during dobutamine stress. Twenty-one segment...
Purpose: This study evaluates the prevalence of cardiac metastases in patients with serotonin pro... more Purpose: This study evaluates the prevalence of cardiac metastases in patients with serotonin producing neuroendocrine tumours (NET), examined with 18 F-FDOPA PET/CT, and the relationship of these metastases to the presence of carcinoid heart disease (CHD) based on echocardiography.
Background: Carotid endarterectomy (CEA) is still considered the "gold-standard" of the treatment... more Background: Carotid endarterectomy (CEA) is still considered the "gold-standard" of the treatment of patients with significant carotid stenosis and has proven its value during past decades. However, endovascular techniques have recently been evolving. Carotid artery stenting (CAS) is challenging CEA for the best treatment in patients with carotid stenosis. This review presents the development of CAS according to early reports, results of recent randomized trials, and future perspectives regarding CAS. Methods: A literature search using the PubMed and Cochrane databases identified articles focusing on the key issues of CEA and CAS.
The purpose of this study was to compare the prognostic value of left ventricular ejection fracti... more The purpose of this study was to compare the prognostic value of left ventricular ejection fraction (LVEF) and myocardial perfusion reserve (MPR) assessed with PET in patients with ischemic heart disease (IHD). Myocardial perfusion is the main determinant of left ventricular function in patients with IHD. The prognostic value of LVEF has been widely established. In addition, MPR determines survival in patients with hypertrophic and dilated cardiomyopathies. In the present study, we evaluated whether MPR also determines survival in patients with IHD. Methods: Between 1995 and 2003, 480 consecutive patients with chronic IHD underwent dipyridamole stress and rest 13 N-ammonia PET to determine MPR. Additionally, 18 F-FDG PET was performed for viability (mismatching defects), infarction (matching defects), and left ventricular function assessment. Patients were followed for all causes of mortality and major cardiovascular events. Results: In 463 of the 480 patients, valid MPR could be measured (368 men; mean age, 66 6 11 y; LVEF, 35% 6 15%). One hundred nineteen patients underwent a PET-driven revascularization (67 through percutaneous coronary intervention and 52 through coronary artery bypass grafting). The remaining 344 patients were the subject of this study. The overall MPR was 1.71 6 0.50 (intertertile boundaries, 1.49 and 1.84). After adjustment for age and sex, MPR was associated with a hazard ratio for cardiac death of 4.11 (95% confidence interval, 2.98-5.67) per SD decrease, whereas the risk for LVEF was 2.76 (2.00-3.82) per SD decrease. Conclusion: Patients with IHD with a low MPR are at high risk of cardiac death. MPR is a more sensitive predictor for cardiac death than is LVEF.
Aims. FDG-PET can be used to identify vulnerable plaques in atherosclerotic disease. Clinical FDG... more Aims. FDG-PET can be used to identify vulnerable plaques in atherosclerotic disease. Clinical FDG-PET camera systems are restricted in terms of resolution for the visualization of detailed inflammation patterns in smaller vascular structures. The aim of the study is to evaluate the possible added value of a high-resolution microPET system in excised carotid plaques using FDG.
European Journal of Vascular and Endovascular Surgery, 2008
Nuclear medicine imaging differs from other imaging modalities by showing physiological processes... more Nuclear medicine imaging differs from other imaging modalities by showing physiological processes instead of anatomical details. To describe the current applications of positron emission tomography (PET) and single photon emission computed tomography (SPECT) as a diagnostic tool for vascular disease as relevant to vascular surgeons. A literature search identified articles focussing on vascular disease and PET or SPECT using the Pubmed database. Manual cross referencing was also performed. PET and SPECT may be used to assess plaque vulnerability, biology of aneurysm progression, prosthetic graft infection, and vasculitis. The ability to combine computerized tomography scanning or magnetic resonance imaging with PET or SPECT adds detailed anatomical information and enhances the potential of nuclear medicine imaging in the investigation of vascular disease. Considerable further information will be needed to define whether and where PET or SPECT will fit in a clinical strategy. The necessary validation studies represent an exciting challenge for the future but also may require the development of interdisciplinary imaging groups to integrate expertise and optimize nuclear diagnostic potential.
European Journal of Vascular and Endovascular Surgery, 2008
Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque for... more Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque formation, which may progress to plaque rupture with subsequent thromboembolic events and/or occlusion of the arterial lumen. There is increasing evidence that the development or progression of atherosclerosis is associated with advanced glycation endproducts (AGEs). AGEs are a heterogeneous group of compounds formed by the non-enzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE strategies. This review summarizes AGE formation and biochemistry, the pathogeneic role of AGEs in cardiovascular disease, anti-AGE therapies and clinical relevance to vascular surgery. Ó
Intrinsic functional properties of high density lipoproteins (HDL) are considered to be physiolog... more Intrinsic functional properties of high density lipoproteins (HDL) are considered to be physiologically important for atheroprotection. We compared the HDL anti-inflammatory capacity between patients with acute myocardial infarction (MI) and patients with non-cardiac chest pain, and prospectively determined the association of new major adverse cardiovascular events (MACE) with this metric of HDL function. A prospective study was carried out in 93 patients referred for acute chest pain (65 patients with acute MI). The HDL anti-inflammatory capacity was determined as the ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 mRNA expression in endothelial cells in vitro. Acute MI at admission was associated with impaired HDL anti-inflammatory capacity (p=0.001), even after adjustment for HDL cholesterol and apolipoprotein A-I (p=0.003). Twenty nine MACE were ascertained during a median follow-up of 1210 (910-1679) days. New MACE was associated with impaired HDL anti-inflammatory capacity (hazard ratio: 1.80 (1.17-2.77) per SD change, p=0.007) in age, sex, HDL cholesterol and apolipoprotein-AI adjusted analysis. The ability of HDL to attenuate endothelial inflammation is impaired in acute MI, and this metric of HDL function may serve as a predictor of new MACE, even independent of HDL cholesterol and apolipoprotein A-I.
Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. Th... more Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.
Background: The cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), play... more Background: The cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), plays a key role in HDL maturation and remodeling. Myeloperoxidase (MPO) may compromise LCAT enzymatic activity. We tested the extent to which plasma LCAT activity is altered in acute myocardial infarction (MI) in conjunction with abnormal MPO levels. We also assessed the impact of LCAT and MPO on newly developed major adverse cardiovascular events (MACE). Methods: Two-hundred one consecutive patients referred for acute chest pain of whom 134 had MI (95 with ST-elevation) participated. Forty-five new MACE were ascertained during 1203 (range 13e1745) days of follow-up among 185 patients. Plasma LCAT activity was measured using an exogenous substrate assay. MPO mass was assayed by chemiluminescent microparticle immunoassay. Results: Plasma LCAT activity was decreased by 15%, coinciding with 7-fold increased MPO levels in acute MI patients vs. patients with non-cardiac chest pain (p < 0.001 for both; correlation: r ¼ À0.343, p < 0.001). MI at admission was associated independently with both lower plasma LCAT activity and higher MPO (age-and sex-adjusted odds ratio per 1 SD increment: 0.46 (95% CI, 0.31e0.68), p < 0.001 and 7.58 (95% CI, 3.34e17.11), p < 0.001, respectively). In an analysis with LCAT and MPO together these associations were modestly attenuated. MPO mass (hazard ratio: 1.59 (95% CI, 1.15e2.19), p ¼ 0.004), but not LCAT activity (hazard ratio: 0.87 (95% CI, 0.65e1.19), p ¼ 0.39), predicted newly manifest MACE. Conclusion: In acute MI patients, plasma LCAT activity is decreased coinciding with increased MPO levels. Higher MPO but not lower LCAT activity prospectively predicts adverse cardiac outcome.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, Jan 16, 2015
In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atheroscler... more In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated. Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense™ 680 and imaged with IVIS® Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages. There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and αSMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages. MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 ra...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014
In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation.... more In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the presence of activated macrophages in human atherosclerotic plaques by (99m)Tc-folate imaging and to evaluate whether this technique can discriminate between an M1-like and M2-like macrophage phenotype. Carotid endarterectomy specimens of 20 patients were incubated with (99m)Tc-folate, imaged using micro-SPECT, and divided into 3-mm slices. The mean accumulation was calculated per slice, and the distribution of M1-like and M2-like macrophages per slice was quantified by immunohistochemical staining for CD86 as well as inducible nitric oxide synthase (iNOS) for M1 and CD163 and FR-β for M2 macrophages. Monocytes from healthy donors were differentiated toward M1-like or M2-like phenotype by in vitro cultu...
Therapy advice based on dual-source computed tomography (DSCT) in comparison with coronary angiog... more Therapy advice based on dual-source computed tomography (DSCT) in comparison with coronary angiography (CAG) was investigated and the results evaluated after 1-year follow-up. Thirty-three consecutive patients (mean age 61.9 years) underwent DSCT and CAG and were evaluated independently. In an expert reading (the "gold standard"), CAG and DSCT examinations were evaluated simultaneously by an experienced radiologist and cardiologist. Based on the presence of significant stenosis and current guidelines, therapy advice was given by all readers blinded from the results of other readings and clinical information. Patients were treated based on a multidisciplinary team evaluation including all clinical information. In comparison with the gold standard, CAG had a higher specificity (91%) and positive predictive value (PPV) (95%) compared with DSCT (82% and 91%, respectively). DSCT had a higher sensitivity (96%) and negative predictive value (NPV) (89%) compared with CAG (91% and 83%, respectively). The DSCT-based therapy advice did not lead to any patient being denied the revascularization they needed according to the multidisciplinary team evaluation. During follow-up, two patients needed additional revascularization. The high NPV for DSCT for revascularization assessment indicates that DSCT could be safely used to select patients benefiting from medical therapy only.
Early detection of myocardial ischemia is of major importance in critical-care medicine. Changes ... more Early detection of myocardial ischemia is of major importance in critical-care medicine. Changes of lactate or glucose levels in the cardial venous efflux may be useful parameters. We succeeded in integrating an ultrafiltration membrane in a cardiac catheter for continuous sampling. The ultrafiltrate was analyzed outside the body, resulting in a lag-time of about 24 min. Biosensors in a flow-injection
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014
In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation.... more In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the presence of activated macrophages in human atherosclerotic plaques by (99m)Tc-folate imaging and to evaluate whether this technique can discriminate between an M1-like and M2-like macrophage phenotype. Carotid endarterectomy specimens of 20 patients were incubated with (99m)Tc-folate, imaged using micro-SPECT, and divided into 3-mm slices. The mean accumulation was calculated per slice, and the distribution of M1-like and M2-like macrophages per slice was quantified by immunohistochemical staining for CD86 as well as inducible nitric oxide synthase (iNOS) for M1 and CD163 and FR-β for M2 macrophages. Monocytes from healthy donors were differentiated toward M1-like or M2-like phenotype by in vitro cultu...
Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, 2009
Background. In idiopathic dilated cardiomyopathy (IDC) an imbalance between myocardial oxygen con... more Background. In idiopathic dilated cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. Subclinical myocardial ischaemia may contribute to progressive deterioration of left ventricular function. The relation between regional myocardial perfusion reserve (MPR) and contractile performance was investigated.Methods. Patients with newly diagnosed IDC underwent positron emission tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dypiridamole stress), and (18)F-fluorodeoxyglucose viability tracer and a dobutamine stress MRI. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17-segment model.Results. Twenty-two patients were included (age 49+/-11 years; 15 males, LVEF 33+/-10%). With MRI, a total of 305 segments could be analysed. Wall motion abnormalities at rest were present in 127 (35.5%) segments and in 103 (29.9%) during dobutamine stress. Twenty-one segment...
Purpose: This study evaluates the prevalence of cardiac metastases in patients with serotonin pro... more Purpose: This study evaluates the prevalence of cardiac metastases in patients with serotonin producing neuroendocrine tumours (NET), examined with 18 F-FDOPA PET/CT, and the relationship of these metastases to the presence of carcinoid heart disease (CHD) based on echocardiography.
Background: Carotid endarterectomy (CEA) is still considered the "gold-standard" of the treatment... more Background: Carotid endarterectomy (CEA) is still considered the "gold-standard" of the treatment of patients with significant carotid stenosis and has proven its value during past decades. However, endovascular techniques have recently been evolving. Carotid artery stenting (CAS) is challenging CEA for the best treatment in patients with carotid stenosis. This review presents the development of CAS according to early reports, results of recent randomized trials, and future perspectives regarding CAS. Methods: A literature search using the PubMed and Cochrane databases identified articles focusing on the key issues of CEA and CAS.
The purpose of this study was to compare the prognostic value of left ventricular ejection fracti... more The purpose of this study was to compare the prognostic value of left ventricular ejection fraction (LVEF) and myocardial perfusion reserve (MPR) assessed with PET in patients with ischemic heart disease (IHD). Myocardial perfusion is the main determinant of left ventricular function in patients with IHD. The prognostic value of LVEF has been widely established. In addition, MPR determines survival in patients with hypertrophic and dilated cardiomyopathies. In the present study, we evaluated whether MPR also determines survival in patients with IHD. Methods: Between 1995 and 2003, 480 consecutive patients with chronic IHD underwent dipyridamole stress and rest 13 N-ammonia PET to determine MPR. Additionally, 18 F-FDG PET was performed for viability (mismatching defects), infarction (matching defects), and left ventricular function assessment. Patients were followed for all causes of mortality and major cardiovascular events. Results: In 463 of the 480 patients, valid MPR could be measured (368 men; mean age, 66 6 11 y; LVEF, 35% 6 15%). One hundred nineteen patients underwent a PET-driven revascularization (67 through percutaneous coronary intervention and 52 through coronary artery bypass grafting). The remaining 344 patients were the subject of this study. The overall MPR was 1.71 6 0.50 (intertertile boundaries, 1.49 and 1.84). After adjustment for age and sex, MPR was associated with a hazard ratio for cardiac death of 4.11 (95% confidence interval, 2.98-5.67) per SD decrease, whereas the risk for LVEF was 2.76 (2.00-3.82) per SD decrease. Conclusion: Patients with IHD with a low MPR are at high risk of cardiac death. MPR is a more sensitive predictor for cardiac death than is LVEF.
Aims. FDG-PET can be used to identify vulnerable plaques in atherosclerotic disease. Clinical FDG... more Aims. FDG-PET can be used to identify vulnerable plaques in atherosclerotic disease. Clinical FDG-PET camera systems are restricted in terms of resolution for the visualization of detailed inflammation patterns in smaller vascular structures. The aim of the study is to evaluate the possible added value of a high-resolution microPET system in excised carotid plaques using FDG.
European Journal of Vascular and Endovascular Surgery, 2008
Nuclear medicine imaging differs from other imaging modalities by showing physiological processes... more Nuclear medicine imaging differs from other imaging modalities by showing physiological processes instead of anatomical details. To describe the current applications of positron emission tomography (PET) and single photon emission computed tomography (SPECT) as a diagnostic tool for vascular disease as relevant to vascular surgeons. A literature search identified articles focussing on vascular disease and PET or SPECT using the Pubmed database. Manual cross referencing was also performed. PET and SPECT may be used to assess plaque vulnerability, biology of aneurysm progression, prosthetic graft infection, and vasculitis. The ability to combine computerized tomography scanning or magnetic resonance imaging with PET or SPECT adds detailed anatomical information and enhances the potential of nuclear medicine imaging in the investigation of vascular disease. Considerable further information will be needed to define whether and where PET or SPECT will fit in a clinical strategy. The necessary validation studies represent an exciting challenge for the future but also may require the development of interdisciplinary imaging groups to integrate expertise and optimize nuclear diagnostic potential.
European Journal of Vascular and Endovascular Surgery, 2008
Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque for... more Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque formation, which may progress to plaque rupture with subsequent thromboembolic events and/or occlusion of the arterial lumen. There is increasing evidence that the development or progression of atherosclerosis is associated with advanced glycation endproducts (AGEs). AGEs are a heterogeneous group of compounds formed by the non-enzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE strategies. This review summarizes AGE formation and biochemistry, the pathogeneic role of AGEs in cardiovascular disease, anti-AGE therapies and clinical relevance to vascular surgery. Ó
Intrinsic functional properties of high density lipoproteins (HDL) are considered to be physiolog... more Intrinsic functional properties of high density lipoproteins (HDL) are considered to be physiologically important for atheroprotection. We compared the HDL anti-inflammatory capacity between patients with acute myocardial infarction (MI) and patients with non-cardiac chest pain, and prospectively determined the association of new major adverse cardiovascular events (MACE) with this metric of HDL function. A prospective study was carried out in 93 patients referred for acute chest pain (65 patients with acute MI). The HDL anti-inflammatory capacity was determined as the ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 mRNA expression in endothelial cells in vitro. Acute MI at admission was associated with impaired HDL anti-inflammatory capacity (p=0.001), even after adjustment for HDL cholesterol and apolipoprotein A-I (p=0.003). Twenty nine MACE were ascertained during a median follow-up of 1210 (910-1679) days. New MACE was associated with impaired HDL anti-inflammatory capacity (hazard ratio: 1.80 (1.17-2.77) per SD change, p=0.007) in age, sex, HDL cholesterol and apolipoprotein-AI adjusted analysis. The ability of HDL to attenuate endothelial inflammation is impaired in acute MI, and this metric of HDL function may serve as a predictor of new MACE, even independent of HDL cholesterol and apolipoprotein A-I.
Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. Th... more Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.
Background: The cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), play... more Background: The cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), plays a key role in HDL maturation and remodeling. Myeloperoxidase (MPO) may compromise LCAT enzymatic activity. We tested the extent to which plasma LCAT activity is altered in acute myocardial infarction (MI) in conjunction with abnormal MPO levels. We also assessed the impact of LCAT and MPO on newly developed major adverse cardiovascular events (MACE). Methods: Two-hundred one consecutive patients referred for acute chest pain of whom 134 had MI (95 with ST-elevation) participated. Forty-five new MACE were ascertained during 1203 (range 13e1745) days of follow-up among 185 patients. Plasma LCAT activity was measured using an exogenous substrate assay. MPO mass was assayed by chemiluminescent microparticle immunoassay. Results: Plasma LCAT activity was decreased by 15%, coinciding with 7-fold increased MPO levels in acute MI patients vs. patients with non-cardiac chest pain (p < 0.001 for both; correlation: r ¼ À0.343, p < 0.001). MI at admission was associated independently with both lower plasma LCAT activity and higher MPO (age-and sex-adjusted odds ratio per 1 SD increment: 0.46 (95% CI, 0.31e0.68), p < 0.001 and 7.58 (95% CI, 3.34e17.11), p < 0.001, respectively). In an analysis with LCAT and MPO together these associations were modestly attenuated. MPO mass (hazard ratio: 1.59 (95% CI, 1.15e2.19), p ¼ 0.004), but not LCAT activity (hazard ratio: 0.87 (95% CI, 0.65e1.19), p ¼ 0.39), predicted newly manifest MACE. Conclusion: In acute MI patients, plasma LCAT activity is decreased coinciding with increased MPO levels. Higher MPO but not lower LCAT activity prospectively predicts adverse cardiac outcome.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, Jan 16, 2015
In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atheroscler... more In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated. Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense™ 680 and imaged with IVIS® Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages. There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and αSMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages. MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 ra...
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