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Biomedical subjects

A C van der Wal

Publications and source records attributed to A C van der Wal.

At least 19 recordsLinked to original sources
PubMed2006

Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction.

BACKGROUND: C reactive protein (CRP), an important serum marker of atherosclerotic vascular disease, has recently been reported to be active inside human atherosclerotic plaques. AIMS: To investigate the simultaneous presence of macrophages, CRP, membrane attack complex C5b-9 (MAC), and oxidised low density lipoprotein (oxLDL) in atherectomy specimens from patients with different coronary syndromes. METHODS: In total, 54 patients with stable angina (SA; n = 21), unstable angina (UA; n = 15), and myocardial infarction (MI; n = 18) underwent directional coronary atherectomy for coronary lesions. Cryostat sections of atherosclerotic plaques were immunohistochemically stained with monoclonal antibodies: anti-CD68 (macrophages), anti-5G4 (CRP), aE11 (MAC), and 12E7 (oxLDL). Immunopositive areas were evaluated in relation to fibrous and neointima tissues, atheroma, and media. Quantitative analysis was performed using image cytometry with systematic random sampling (percentage immunopositive/total tissue area). RESULTS: Macrophages, CRP, MAC, and oxLDL were simultaneously present in a higher proportion of fibrous tissue and atheroma of atherectomy specimens from patients with UA and MI compared with SA (p<0.05). Quantitative analysis showed significantly higher mean percentages of macrophages in plaques from patients with MI (44%) than UA (30%; p<0.01) and SA (20%; p<0.001). Significantly higher mean percentages of CRP were also seen in MI (25%) and UA (25%) compared with SA (12%; p<0.05). CONCLUSIONS: The presence of CRP, complement, and oxLDL in a high proportion of plaque tissue from patients with unstable coronary artery disease implies that these surrogate markers have important proinflammatory effects inside atherosclerotic plaques. This may increase vulnerability to plaque rupture and thrombosis, with subsequent clinical sequelae.

Angina Pectoris↗
PubMed2005

Pre-procedural ACE-activity does not predict symptomatic in-stent restenosis.

BACKGROUND: Several studies indicate that ACE-activity is related to atherosclerosis. We investigated the correlation between ACE-activity, in plasma as well as in the atherosclerotic plaque, and in-stent restenosis. METHODS AND RESULTS: ACE-activity was measured in blood samples from 178 patients who underwent a percutaneous coronary intervention with stent placement. During 8 months follow-up, 51 of these patients had an adverse clinical event. ACE-activity did not differ between patients with or without adverse events (21.5 vs. 23.1 nM/ml/min; P=0.36). Tissue samples were obtained with an atherectomy catheter before elective stent placement in another group of 13 patients with de novo stenosis. In this tissue, we determined the ACE-content immunohistologically. These patients were scheduled for follow-up quantitative coronary angiography after 12 months. In this group, the quantity of ACE was not correlated to the late luminal loss (0.31 vs. 0.38 mm; P=0.76). CONCLUSION: In this study, pre-procedural ACE-activity, in plasma as well as in the atherosclerotic plaque, does not predict the occurrence of in-stent restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2005

The role of shear stress in the generation of rupture-prone vulnerable plaques.

Blood-flow-induced shear stress acting on the arterial wall is of paramount importance in vascular biology. Endothelial cells sense shear stress and largely control its value in a feedback-control loop by adapting the arterial dimensions to blood flow. Nevertheless, to allow for variations in arterial geometry, such as bifurcations, shear stress control is modified at certain eccentrically located sites to let it remain at near-zero levels. In the presence of risk factors for atherosclerosis, low shear stress contributes to local endothelial dysfunction and eccentric plaque build up, but normal-to-high shear stress is atheroprotective. Initially, lumen narrowing is prevented by outward vessel remodeling. Maintenance of a normal lumen and, by consequence, a normal shear stress distribution, however, prolongs local unfavorable low shear stress conditions and aggravates eccentric plaque growth. While undergoing such growth, eccentric plaques at preserved lumen locations experience increased tensile stress at their shoulders making them prone to fissuring and thrombosis. Consequent loss of the plaque-free wall by coverage with thrombus and new tissue may bring shear-stress-controlled lumen preservation to an end. This change causes shear stress to increase, which as a new condition may transform the lesion into a rupture-prone vulnerable plaque. We present a discussion of the role of shear stress, in setting the stage for the generation of rupture-prone, vulnerable plaques, and how this may be prevented.

Arteriosclerosis↗
PubMed2005

The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications.

American Heart Association type IV plaques consist of a lipid core covered by a fibrous cap, and develop at locations of eccentric low shear stress. Vascular remodeling initially preserves the lumen diameter while maintaining the low shear stress conditions that encourage plaque growth. When these plaques eventually start to intrude into the lumen, the shear stress in the area surrounding the plaque changes substantially, increasing tensile stress at the plaque shoulders and exacerbating fissuring and thrombosis. Local biologic effects induced by high shear stress can destabilize the cap, particularly on its upstream side, and turn it into a rupture-prone, vulnerable plaque. Tensile stress is the ultimate mechanical factor that precipitates rupture and atherothrombotic complications. The shear-stress-oriented view of plaque rupture has important therapeutic implications. In this review, we discuss the varying mechanobiologic mechanisms in the areas surrounding the plaque that might explain the otherwise paradoxical observations and unexpected outcomes of experimental therapies.

Arterial Occlusive Diseases↗
PubMed2002

Sudden unexpected death in young adults. Discrepancies between initiation of acute plaque complications and the onset of acute coronary death.

AIMS: To study the time relationship between the onset of coronary thrombosis and sudden unexpected cardiac death in young adults. METHODS AND RESULTS: Hearts of 11 young adults (< or = 35 years), who had died within 1h after onset of symptoms and presented with a coronary thrombotic occlusion were studied retrospectively for the type of underlying plaque complication and the time of onset of thrombus formation. In all cases tissue blocks were taken from the occluded artery and sectioned for microscopic evaluation. Of 11 culprit lesions 10 were mainly fibrocellular; only one was lipid-rich. Inflammatory cells were found in all plaques, albeit in highly variable amounts. Plaque erosion had occurred in nine; deep ruptures in two. Analysis of the plaque-related occluding thrombus revealed fresh thrombosis in three (both ruptured plaques and one erosion); the other eight, however, showed occlusion with different histological stages of organization of thrombus. CONCLUSIONS: Despite strict inclusion criteria for sudden death in these young adults, the majority must have had plaque instability for some time, since thrombus formation had occurred at least days to weeks prior to the acute event.

Acute Disease↗
PubMed2001

Adventitial infiltrates associated with advanced atherosclerotic plaques: structural organization suggests generation of local humoral immune responses.

Advanced atherosclerotic lesions often contain adventitial lymphoid infiltrates, which occasionally contain nodular aggregates resembling lymphoid follicles. The structural organization suggests that local maturation of B cells may take place at these sites, as described for the mucosa-associated lymphoid tissue (MALT). This concept was evaluated by studying the micro-anatomy and cellular composition of adventitial infiltrates associated with advanced atherosclerosis of the aorta. Sections of 22 atherosclerotic aortas were stained immunohistochemically for cellular markers characteristic for lymphoid follicles, such as HECA-452-positive endothelial cells, CD20-positive B cells, CD21-positive follicular dendritic cells, and CD68-positive macrophages. Ki-67 was used as a proliferation marker. The TUNEL technique was used to study the presence of apoptotic cells. Specimens containing MALT served as comparison and positive controls. Seven of the 22 atherosclerotic aortas contained adventitial infiltrates resembling lymphoid follicles. The organized nodular centres were composed of CD45RA+ B cells, follicular dendritic cells (CD21+), a few T lymphocytes (CD3+) and 'tingible body' macrophages (CD68+). A large number of cells were Ki-67-positive; apoptotic bodies were numerous and phagocytosed by macrophages. The parafollicular area contained CD45RO-positive T cells and HECA-452-positive vessels. Vessels elsewhere were always HECA-452-negative. Specimens with MALT showed similar features. This study reveals a close resemblance between adventitial lymphoid infiltrates in advanced atherosclerotic aortic disease and MALT, suggesting local generation of a humoral immune response, likely to be initiated by antigens released during a process of long-standing tissue injury and inflammation as part of advanced atherosclerosis.

Adult↗
PubMed2001

Histologic evaluation of skin damage after overlapping and nonoverlapping flashlamp pumped pulsed dye laser pulses: A study on normal human skin as a model for port wine stains.

BACKGROUND AND OBJECTIVE: In the treatment of port wine stains (PWS) with the flashlamp pumped pulsed dye laser (FPPDL), no consensus exists about overlapping of pulses. The advantage of overlapping pulses is homogeneous lightening of the PWS; the risk is redundant tissue damage. The aim of this study was to determine the histopathologic effect on human skin of pulsed dye laser pulses with various degrees of overlap, with normal human skin as a model for PWS. STUDY DESIGN/MATERIALS AND METHODS: Eighteen healthy white volunteers were irradiated with pulsed dye laser pulses with increasing radiant exposure and with different degrees of overlap. Biopsy samples were taken and histologically analysed. RESULTS: Overlapping of pulses on normal human skin enhances depth of vascular damage with approximately 30%. Adjacent pulses also show this effect. We found no histologic signs of serious damage to epidermis or dermal connective tissue by using radiant exposure levels of 6-8 J/cm(2), regardless of pulse application. CONCLUSIONS: Reasoning that the mechanism of tissue injury is comparable for normal and PWS skin, we conclude that it is safe to treat PWS with overlapping FPPDL pulses to achieve homogeneous lightening.

Abdomen↗
PubMed2001

Angiogenesis three months after clinical transmyocardial laser revascularization using an excimer laser.

BACKGROUND AND OBJECTIVE: We present for the first time histologic findings 3 months after clinical transmyocardial laser revascularization using a XeCl excimer laser. STUDY DESIGN/MATERIALS AND METHODS: Histology was performed on a patient who died from a noncardiac cause 3 months post-excimer TMLR. RESULTS: In the treated myocardium, no patent channels were found but scars were seen with a linear distribution and in continuity with circumscribed small fibrotic endocardial and epicardial scars. The scars were highly vascularized by new vessels, ranging from small capillaries to large thin walled, and sometimes branching ectatic vessels. Sprouting of vessels into the adjacent myocardium was also observed. CONCLUSION: These results suggest that angiogenesis might play a role in the clinical improvement after TMLR.

Aged↗
PubMed2001

Recurrent unstable angina after directional coronary atherectomy is related to the extent of initial coronary plaque inflammation.

OBJECTIVES: This study was performed to evaluate the relationship between plaque inflammation of the initial culprit lesion and the incidence of recurrent angina for one year after directional coronary atherectomy (DCA). BACKGROUND: A positive correlation between coronary plaque inflammation and angiographic restenosis has been reported. METHODS: A total of 110 patients underwent DCA. Cryostat sections were immunohistochemically stained with monoclonal antibodies CD68 (macrophages), CD-3 (T lymphocytes) and alpha-actin (smooth muscle cells [SMCs]). The SMC and macrophage contents were planimetrically quantified as a percentage of the total tissue area. T lymphocytes were counted as the number of cells/mm2. The patients were followed for one year to document recurrent unstable angina pectoris (UAP) or stable angina pectoris (SAP). RESULTS: Recurrent UAP developed in 16 patients, whereas recurrent SAP developed in 17 patients. The percent macrophage areas were larger in patients with recurrent UAP (27 +/- 12%) than in patients with recurrent SAP (8 +/- 4%; p = 0.0001) and those without recurrent angina (18 +/- 14%; p = 0.03). The number of T lymphocytes was also greater in patients with recurrent UAP (25 +/- 14 cells/mm2) than in patients with recurrent SAP (14 +/- 8 cells/mm2; p = 0.02) and those without recurrent angina (14 +/- 12 cells/mm2; p = 0.002). Multiple stepwise logistic regression analysis identified macrophage areas and T lymphocytes as independent predictors for recurrent UAP. CONCLUSIONS: There is a positive association between the extent of initial coronary plaque inflammation and the recurrence of unstable angina during long-term follow-up after DCA. These results underline the role of ongoing smoldering plaque inflammation in the recurrence of unstable angina after coronary interventions.

Aged↗
PubMed2001

Cardiac pathology in neuronal ceroid lipofuscinoses--a clinicopathologic correlation in three patients.

We report the clinical details and the pathology of the heart at autopsy of three neuronal ceroid lipofuscinosis (NCL) patients. Two patients were diagnosed as classical juvenile NCL and one as a variant juvenile NCL (JNCL) with granular osmiophilic deposits (GRODs). Cardiac findings during life were retrospectively evaluated and included left ventricular hypertrophy with repolarization disturbances (ECG findings) in two patients with classical JNCL and severe bradycardia with periods of sinus arrest in one of them, severe supraventricular tachycardias during anaesthesia in the variant JNCL-patient. At autopsy myocardial and valvular storage of lipopigments, diagnostic for NCL, was observed histologically and confirmed ultrastructurally in all three cases. In two patients with JNCL the storage was associated with hypertrophy and dilation of both ventricles, degenerative myocardial changes, interstitial fibrosis and fatty replacement. Abundant accumulation and degeneration were seen in all components of the conduction system in three patients, which outreached at several places by far the storage of the adjacent myocardium. Our observations indicate a prominent involvement of the heart in NCL, with preference of storage for the conduction system of the heart.

Adult↗
PubMed2001

Renal vascular changes in renal disease independent of hypertension.

INTRODUCTION: Cardiovascular disease is common in patients with renal disease, but little is known about the effect of renal disease and loss of renal function on vascular morphology. Intima proliferation of small renal arteries, which correlates with atherosclerosis in the aorta, is sometimes present in renal disease and has been shown to increase with age and hypertension. We studied the effect of chronic renal disease and renal function, independent of hypertension, on intima proliferation. METHODS: We retrospectively selected renal biopsies of subjects in whom a glomerular filtration rate (GFR) measurement with [(125)I] iothalamate had been performed. To separate the effects of renal disease and renal function, we selected biopsies from (A) normotensive controls undergoing nephrectomy because of renal carcinomas; (B) normotensive patients with renal disease and GFR > 90 ml/min; (C) normotensive patients with GFR 30-90 ml/min, and (D) hypertensive patients with a GFR < 90 ml/min. The area of the arteriolar lumen, intima, and media were measured. RESULTS: No significant changes from control subjects were observed in group B. Intima proliferation was observed when renal function declined (intima/total vessel surface ratio was 0.262 +/- 0.071 in group C, 0.192 +/- 0.032 in group A, and 0.205 +/- 0.035 in group B, P < 0.05). The intima proliferation was aggravated in patients with renal insufficiency and hypertension (0.333 +/- 0.121, P < 0.05). Media surface area was not different between groups. CONCLUSION: Renal disease with preserved GFR does not cause significant intima proliferation of small renal arteries. Loss of renal function is accompanied by intima proliferation, even in the absence of systemic hypertension.

Adult↗
PubMed2001

Immunohistochemical detection of interferon-gamma: fake or fact?

Immunohistochemistry is a widely accepted tool to investigate the presence and immunolocalization of cytokines in tissue sections at the protein level. We have tested the specificity and reproducibility of IFNgamma immunohistochemistry on tissue sections with a large panel of anti-IFNgamma antibodies. Thirteen different commercially available anti-IFNgamma antibodies, including seven advertised and/or regularly applied for immunohistochemistry/-cytochemistry, were tested using a three-step streptavidin-biotin-peroxidase technique and a two-step immunofluorescence (FACS) analysis. Immunoenzyme double staining was used to identify the IFNgamma-positive cells. Serial cryostat sections were used of human reactive hyperplastic tonsils, rheumatoid synovium, and inflammatory abdominal aortic aneurysms, known to possess a prominent Th1-type immune response. In vitro phorbol myristate acetate/ionomycin-stimulated T-cells served as positive control; unstimulated cells served as negative control. Cultured T-cells were used adhered to glass slides (immunocytochemistry), in suspension (FACS), or snap-frozen and sectioned (immunohistochemistry). Immunocytochemistry and FACS analysis on stimulated cultured T-cells showed positive staining results with 12 of 13 anti-IFNgamma antibodies. However, immunohistochemistry of sectioned stimulated T-cells was negative with all. Unstimulated cells were consistently negative. IFNgamma immunohistochemical single- and double staining analysis of the tissue sections showed huge variations in staining patterns, including positivity for smooth muscle cells (n = 8), endothelial cells (n = 4), extracellular matrix (n = 4), and CD138+ plasma cells (n = 12). Specific staining of T-cells, as the sole positive staining, was not achieved with any of the 13 antibodies. IFNgamma-immunohistochemistry appears unreliable because of lack of specificity to stain T-cells in situ. In fact, depending on the type of anti-IFNgamma antibody used, a variety of different cell constituents were nonspecifically stained. Consequently, data based on IFNgamma-immunohistochemistry must be interpreted with great caution.

Aged↗
PubMed2000

Plaque inflammation in restenotic coronary lesions of patients with stable or unstable angina.

OBJECTIVES: To evaluate immunohistochemically various parameters of inflammation in coronary atherectomy specimens obtained from restenotic culprit lesions of patients presenting with either stable or unstable angina (UA). BACKGROUND: There is no information regarding the relationship between atherosclerotic plaque inflammation and the severity of the coronary syndromes in patients with restenotic coronary lesions. METHODS: A total of 37 patients with either stable angina or UA underwent directional coronary atherectomy for restenotic coronary lesions. Cryostat sections of atherectomy specimen were immunohistochemically stained with monoclonal antibodies CD68 (macrophages [MACs]), CD3 (T-lymphocytes) and alpha-actin (smooth muscle cells [SMCs]). Smooth muscle cell contents and MAC contents were planimetrically quantified as the percentage immunopositive tissue area of the total tissue area. T-lymphocytes were counted at 100-X magnification throughout the entire section and expressed as number of cells per mm2. RESULTS: Restenotic coronary lesions of patients with UA or stable angina showed no significant difference in SMC areas (31.9%+/-16.3% vs. 38.5%+/-18.8%, respectively; p = NS). However, restenotic coronary lesions of patients presenting with unstable angina contained significantly more MACs (24.4%+/-15.1% vs. 10.5%+/-5.8%, p = 0.001) and T-lymphocytes (18.8 cells/mm2+/-15.1 cells/mm2 vs. 8.6 cells/mm2+/-9.8 cells/mm2; p = 0.034) than patients with stable angina. CONCLUSIONS: These results suggested that inflammation appears to affect plaque instability in restenotic coronary lesions resulting in unstable coronary syndromes.

Adult↗
PubMed2000

Atherosclerosis, inflammation, and infection.

In recent years, it has been shown that inflammation plays an important role in the pathogenesis of atherosclerosis. Activated macrophages, T lymphocytes, and mast cells are present in atherosclerotic plaques, which has led to the notion that the inflammatory response is an immune-mediated process. Complicated lesions, moreover, appear to be associated with an increase in the amount of the inflammatory response and in these patients, increased levels of acute phase proteins are present. The appreciation that atherosclerosis is an immune-mediated inflammatory disease has also led to renewed interest in the potential role of infectious agents in initiating or modulating atherosclerosis. Seroepidemiological studies have shown raised antibody titres against several micro-organisms. However, as yet, there are hardly any data available that provide a sound scientific basis for an infectious origin. Of all potential candidate organisms, Chlamydia pneumoniae appears as the one most likely involved in atherogenesis. C. pneumoniae has been retrieved from atherosclerotic tissues; the level of raised plasma titres correlates with the severity of symptomatic atherosclerotic disease; and the incidence of C. pneumoniae-responsive T cells in peripheral blood is increased in patients with coronary heart disease. It also appears that in some patients T cells generated from atherosclerotic plaques respond to C. pneumoniae. At the present state of knowledge, however, it is fair to state that the relationship between infection, intraplaque inflammation, and atherosclerosis still remains hypothetical, despite the increasing evidence that such a relationship could exist.

Acute-Phase Proteins↗
PubMed2000

Metallothionein in human atherosclerotic lesions: a scavenger mechanism for reactive oxygen species in the plaque?

Oxidative stress is important in the genesis of atherosclerotic lesions. The extracellular effects of reactive oxygen species (ROS), such as oxidative modification of lipoproteins and upregulation of matrix degrading enzymes, are considered crucial in this context. The effects of ROS are counteracted by antioxidant scavenging systems; metallothioneins (MTs) may serve as such. This study was designed to see whether MTs occur in human atherosclerotic plaques and which cell types are involved. The immunohistochemical study focuses on smooth muscle cells (SMCs), macrophages, and T cells. MT immunoreactivity was seen only within SMCs, which occurred usually in small clusters and were found mostly near lipid cores and occasionally in the media. Double immunostaining showed MT-positive SMCs and matrix metalloproteinase (MMP)-9 in the same area but not within the same cell. Electron microscopy was done to evaluate the subtype of MT-positive cells and revealed that the majority consisted of synthetic SMCs. Thus, atherosclerotic plaques in humans contain MT known to act as a scavenger for ROS. The observation that MT was expressed only in SMCs, particularly those of synthetic phenotype, suggests that MT plays a role in protecting these active matrix-producing cells.

Arteriosclerosis↗