Biomedical subjects

C M van der Loos

Publications and source records attributed to C M van der Loos.

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↗

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

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

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

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↗

PubMed2000

Double staining of intracellular cytokine proteins and T-lymphocyte subsets. Evaluation of the method in blood and bronchoalveolar lavage fluid.

An immunocytochemical staining method has been developed for simultaneous staining of both cell surface markers (CD4 and CD8) and intracellular cytokine proteins IFN-gamma, IL-4 and IL-5. Cell surface molecules were visualized with alkaline phosphatase, which was developed by Fast Blue BB. Intracellular cytokine proteins were detected by amino-ethyl carbazole. We applied this technique to T cells from T-cell lines and T-cell clones, peripheral blood mononuclear cells and broncho-alveolar lavage fluid cells. Cells were used either unstimulated or stimulated for 4 h with 1 ng/ml PMA and 1 microg/ml ionomycin, which proved to be an optimal stimulus taking cytokine staining, cell recovery and cell viability into account. We studied peripheral blood mononuclear cells from healthy subjects and found that without in vitro stimulation on average 0.4% of the cells were IFN-gamma positive cells. In unstimulated broncho-alveolar lavage fluid cells of the 2 allergic asthmatic subjects studied so far we found higher numbers of cytokine-positive cells (up to 22% of the lymphocytes being IL-4+ cells). By in vitro stimulation, the numbers of cytokine-positive peripheral blood mononuclear cells from the healthy subjects were increased to maximally 5% IFN-gamma+ cells. In stimulated lavage fluid cells from allergic asthmatic subjects maximally 34% of the lymphocytes became IFN-gamma+. We conclude that this method allows detection of intracellular cytokine proteins in both CD4+ and CD8+ T cells without the need for stimulating the cells in vitro. In vitro stimulation may change the cytokine profile detected.

Adult↗

PubMed2000

The animal research kit (ARK) can be used in a multistep double staining method for human tissue specimens.

The newly developed Animal Research Kit (ARK) offers a simple and economic way of biotinylating mouse primary antibodies for background-free immunostaining of mouse and rat tissue specimens. Biotinylation involves the use of a biotinylated goat anti-mouse immunoglobulin Fab fragment mixed with a mouse primary antibody and subsequent blocking with normal mouse immunoglobulin. Because a reliable immunoenzyme double staining procedure on human tissue specimens with two unlabeled mouse primary antibodies of identical subclass is almost impossible, we have tested the performance of ARK biotinylation of one primary antibody in a multistep indirect/direct staining protocol. The multistep double staining procedure involved the subsequent application of an unlabeled mouse monoclonal antibody (MAb) 1 detected with an enzyme-labeled EnVision reagent, normal mouse serum for blocking, followed by a biotinylated mouse MAb 2 and enzyme-labeled streptavidin. Alkaline phosphatase and peroxidase enzymatic activities were developed last. Double staining results obtained with an ARK biotinylated reagent were compared with a truly biotinylated reagent using N-hydroxy succinimide-biotin for conjugation. It appeared that both biotinylation procedures revealed identical double staining results. Although a limited number of antibody combinations have been tested, it is clear that this double staining procedure will be successful for many antibody pairs.

Animals↗

PubMed1999

Complete chromogen separation and analysis in double immunohistochemical stains using Photoshop-based image analysis.

Simultaneous detection of two different antigens on paraffin-embedded and frozen tissues can be accomplished by double immunohistochemistry. However, many double chromogen systems suffer from signal overlap, precluding definite signal quantification. To separate and quantitatively analyze the different chromogens, we imported images into a Macintosh computer using a CCD camera attached to a diagnostic microscope and used Photoshop software for the recognition, selection, and separation of colors. We show here that Photoshop-based image analysis allows complete separation of chromogens not only on the basis of their RGB spectral characteristics, but also on the basis of information concerning saturation, hue, and luminosity intrinsic to the digitized images. We demonstrate that Photoshop-based image analysis provides superior results compared to color separation using bandpass filters. Quantification of the individual chromogens is then provided by Photoshop using the Histogram command, which supplies information on the luminosity (corresponding to gray levels of black-and-white images) and on the number of pixels as a measure of spatial distribution. (J Histochem Cytochem 47:119-125, 1999)

Actins↗

PubMed1998

Distribution of inflammatory cells in atherosclerotic plaques relates to the direction of flow.

BACKGROUND: The distribution of macrophages and smooth muscle cells (SMCs) within atherosclerotic plaques is highly variable. This is clinically relevant because these cell types have opposite effects on the stability of atherosclerotic plaques. The present study was designed to investigate whether local variations in arterial flow over the plaque surface could relate to differences in the distribution of SMCs and macrophages in plaques. METHODS AND RESULTS: Thirty-three entire carotid plaques were collected at autopsy and marked at their proximal (in relation to the direction of the blood flow) ends, and the cell composition of upstream parts (where high flow and high shear prevail) was compared with that of downstream parts (low flow and low shear stress). Seventy percent of plaques showed more SMCs in their downstream part, and 67% of plaques contained more macrophages in the upstream part. Immunostained macrophage areas were larger in upstream parts (P=0. 011). Immunostained SMC areas were larger in downstream parts (P=0. 031). Rupture sites of 6 of 9 ruptured plaques were in the upstream part. CONCLUSIONS: Significant differences in cell composition between upstream and downstream parts of plaques indicate a role for arterial flow in the distribution of different cell types. The low-flow/low-shear downstream areas of plaques contain significantly more SMCs, which could provide the background for slowly progressive growth at distal ends of plaques. The significantly high number of macrophages in the upstream areas suggests a relationship between high flow/high shear and plaque instability.

Adult↗

PubMed1998

Mast cell infiltration in acute coronary syndromes: implications for plaque rupture.

OBJECTIVES: To define the role of mast cells in plaque destabilization. BACKGROUND: Inflammation is an essential feature of human coronary plaques. Macrophages and T lymphocytes are considered to contribute to destabilization of the plaques. The role of mast cells in this setting is less well studied. We therefore counted the mast cells in coronary atherectomy specimens from patients with chronic stable angina, unstable angina and severe unstable angina. METHODS: Patients studied had chronic stable angina (group 1, n=11), "stabilized" unstable angina (group 2; Braunwald's class I and II, n=11) and "refractory" unstable angina (group 3; Braunwald's class III, n=7). Samples of culprit lesions (n=29) were obtained by directional atherectomy, snap-frozen and analyzed immunohistochemically. The numbers of mast cells and T lymphocytes per square millimeter squared were counted and the areas containing macrophages and smooth muscle cells were measured by computed planimetry. RESULTS: We found that the numbers of mast cells and T lymphocytes increased from group 1 through groups 2 to 3. Specimens from group 3 also contained the largest numbers of tumor necrosis factor alpha (TNF-alpha)-positive mast cells and of matrix metalloproteinase (MMP)-9 (92 kD gelatinase)-positive macrophages. CONCLUSIONS: Unstable coronary syndromes are associated with increased numbers of mast cells in culprit lesions. Activated mast cells secrete neutral proteases capable of degrading the extracellular matrix and TNF-alpha, capable of stimulating macrophages to synthesize MMP-9. Our observations suggest that mast cells, in addition to macrophages, contribute to matrix degradation and, hence, to progression of coronary syndromes.

Adult↗

PubMed1998

Recent activation of the plaque immune response in coronary lesions underlying acute coronary syndromes.

OBJECTIVE: To discriminate between chronic inflammation and acute activation of the plaque immune response in culprit lesions of patients with acute coronary syndromes. DESIGN: Retrospective study. SETTING: Tertiary referral centre. SUBJECTS: 71 patients having coronary atherectomy were classified according to their ischaemic syndrome: stable angina (n = 23); stabilised unstable angina (n = 18); refractory unstable angina (n = 11); and acute myocardial infarction (n = 19). MAIN OUTCOME MEASURES: Immunohistochemical measurement of interleukin 2 receptor (IL-2R) (CD25) positive cells expressed as a percentage of the total amount of (CD3 positive) T lymphocytes in frozen sections of atherectomy specimens. RESULTS: The number of lesions containing IL-2R (CD25) positive T cells increased with severity of the ischaemic coronary syndrome (stable angina, 52%; stabilised unstable angina, 77.8%; refractory unstable angina, 90.9%; acute myocardial infarction, 89.4%). The percentage of activated T cells (CD25/CD3 ratios x100) increased in lesions associated with refractory unstable angina (7.8%) and acute myocardial infarction (18.5%), compared with those in lesions associated with either chronic stable angina (2.2%) or stabilised unstable angina (3.3%). CONCLUSIONS: An increase in the percentage of IL-2R positive T lymphocytes in culprit lesions of patients with acute coronary syndromes indicates recent activation and amplification of the immune response within plaques. This may result in a burst of inflammatory products with tissue degrading and vasoactive properties and, hence, could initiate or accelerate the onset of an acute coronary event.

Angina Pectoris↗

PubMed1997

Costimulatory molecules in human atherosclerotic plaques: an indication of antigen specific T lymphocyte activation.

Atherosclerotic plaques contain inflammation, composed largely of macrophages and lymphocytes. A proportion of lymphocytes shows signs of activation, but the question arises whether they are activated in an antigen specific way. The expression of costimulatory molecules-receptors that provide accessory signals during antigen-specific activation is a prerequisite for such a condition. This aspect of inflammation in atherosclerotic lesions has not been investigated. Human arterial segments with diffuse intimal thickening, fatty streaks and atherosclerotic plaques were studied with immuno-single and double staining methods. Macrophages and T lymphocytes were stained with CD68 and CD3, respectively, and pan-B cell markers CD19 and CD22 were also used. Costimulatory molecules B7-1 and B7-2, together with their common ligand CD28, and CD27 with its ligand CD70, were stained with specific monoclonal antibodies. The results show that most T lymphocytes were CD27 positive and that only a subpopulation of these (5-15%) was positive also for B7-1, CD28 and CD70. Macrophages expressed B7-1, B7-2, CD28 and CD70, while macrophages positive for CD28 and CD70 have not been reported yet. The expression of costimulatory molecules was most pronounced in the superficial layers at the fibrous cap, but decreased towards the lipid core. This study shows, therefore, that atherosclerotic plaques provide costimulatory signals generally accepted as a prerequisite for adequate T cell stimulation. In addition, this study reveals that only approximately 5-15% of the lymphocytes appears actively involved in the inflammatory reaction.

Aged↗

PubMed1996

C-type natriuretic peptide in human coronary atherosclerotic lesions.

BACKGROUND: C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family and is considered to have regulatory effects on vascular tone and smooth muscle growth. Since these features play a role in atherogenesis, the presence of CNP at such sites was studied. METHODS AND RESULTS: Thirty-three coronary artery segments were harvested at autopsy: 10 normal, with diffuse intimal thickening, and 23 atherosclerotic lesions. Samples were snap-frozen and processed for immunohistochemical staining. For the identification of CNP, a mouse monoclonal antibody (KY-CNP-1) was used. 1A4, EBM-11 (CD68), and von Willebrand factor antibodies were used to stain smooth muscle cells, macrophages, and endothelial cells, respectively. CNP is present in several cell types. Normal arterial segments show CNP-positive endothelial cells. Hypercellular atherosclerotic lesions show distinct CNP positivity of smooth muscle cells and macrophages but a decrease in positivity of endothelial cells. Advanced atherosclerotic lesions contain CNP-positive macrophages, but the smooth muscle cells within the fibrous cap and the surface endothelial cells are almost all CNP-negative. CONCLUSIONS: These observations suggest that CNP has functional significance in atherogenesis.

Adolescent↗

PubMed1996

Solar-simulated ultraviolet irradiation induces selective influx of CD4+ T lymphocytes in normal human skin.

The proportion and composition of the human cutaneous CD3+ T lymphocyte population was determined in situ following a single exposure to physiological, erythema-inducing doses of simulated solar radiation, mainly consisting of UV radiation. Biopsies were taken 1, 2 and 7 days after local irradiation of normal volunteers with 1, 2 and 4 MED by a xenonarc lamp and immunohistochemistry was performed on cryostat sections. Ultraviolet radiation caused an initial decrease of intraepidermal CD3+ T-cell numbers or even could lead to T-cell depletion 24 and 48 h postirradiation, and this was followed by an infiltration of T cells in the epidermis as determined 1 week after UV exposure. The number of dermal CD3+ T cells was increased 24 h after irradiation, reached a maximum at 48 h and subsequently declined at day 7, though remained significantly higher than the unirradiated control. Double staining demonstrated that the CD3+ T cells, which immigrated into the (epi)dermis upon UV exposure, coexpressed CD4 but not CD8. Therefore the CD4/CD8 ratio in skin was markedly increased during the first week upon UV exposure. Our time course study shows that UV radiation affects the T-cell population within human skin by depleting the majority of epidermal T cells and initiating a selective influx of CD4+ T cells.

Adolescent↗

PubMed1996

Expression of platelet derived growth factor B chain and beta receptor in human coronary arteries after percutaneous transluminal coronary angioplasty: an immunohistochemical study.

OBJECTIVE: To evaluate whether expression of platelet derived growth factor B (PDGF-B) protein is associated with expression of its receptor protein in human coronary arteries after angioplasty and to identify cells involved. BACKGROUND: PDGF is considered an important growth factor in the repair process of the vessel wall after angioplasty. In situ hybridisation has revealed expression of PDGF-A and -B chain messenger ribonucleic acid (mRNA) in human coronary arteries at sites of postangioplasty injury. METHODS: Target and non-target sites of eight coronary arteries were studied immunohistochemically for PDGF-B and PDGF-beta receptor proteins in relation to macrophages, T lymphocytes, smooth muscle cells, and HLA-DR positive cells. RESULTS: The PDGF-B and PDGF-beta receptor proteins were expressed in areas with distinct repair, containing alpha actin negative spindle cells, macrophages and, at later stages, alpha actin positive smooth muscle cells as well. When the neointima was composed mainly of alpha actin smooth muscle cells, PDGF-B expression was rare and PDGF-beta receptor expression was negative. CONCLUSIONS: There is expression of PDGF-B and PDGF-beta receptor proteins at sites of postangioplasty repair in human coronary arteries. The associated cells are mainly macrophages and alpha actin negative spindle cells; the latter may be dedifferentiated smooth muscle cells. A link between PDGF expression and the postangioplasty time interval suggests a relation with cell differentiation as part of the maturation of the repair tissue. Mutual expression of both the growth factor and its receptor protein strongly suggests that in humans a PDGF mediated repair process occurs, with involvement of smooth muscle cells and macrophages.

Aged↗

PubMed1996

Clinically stable angina pectoris is not necessarily associated with histologically stable atherosclerotic plaques.

OBJECTIVE: To investigate the extent of plaque inflammation in culprit lesions of patients with chronic stable angina. DESIGN: Retrospective study. SETTING: Amsterdam reference centre. SUBJECTS: 89 consecutive patients who underwent directional coronary atherectomy, 58 of whom met the following inclusion criteria: chronic stable angina (Canadian Cardiovascular Society classification 1-3 (group 1, n = 28)); unstable angina (Braunwald class II (group 2, n = 18)); unstable angina (Braunwald class III (group 3, n = 12)). INTERVENTIONS: Directional atherectomy in patients with angina pectoris. MAIN OUTCOME MEASURES: Tissue areas of culprit lesions occupied by inflammatory cells and smooth muscle cells related to clinically defined ischaemic syndrome. RESULTS: Areas (% of total surface area (mean (SEM)) rich in smooth muscle cells were larger in patients with chronic stable angina (group 1, 51.2 (20.9)) than in those with unstable angina (group 2, 42.1 (20.5); group 3, 29.5 (19.4)) (1 v 2 and 2 v 3, NS; 1 v 3, P < 0.004). Macrophage rich areas were significantly smaller in patients with stable angina (group 1, 21.8 (11.9)) than in those with unstable angina (group 2, 31.5 (14.6); group 3, 46.4 (16.7)) (1 v 2, P < 0.02; 2 v 3, P < 0.02; 1 v 3, P < 0.001). Mean numbers of T cells per mm2 were as follows: group 1, 17 (9.4); group 2, 25 (15.9); group 3, 41 (30.6) (1 v 2, P 0.04; 2 v 3, P 0.07; 1 v 3, P < 0.001). Areas with HLA-DR positive cells showed the same pattern as macrophages and T cells and were smaller in stable (29.9 (12.4)) than in unstable angina (group 2, 40.4 (17.6); group 3, 52.4 (12.0)) (1 v 2, P < 0.02; 2 v 3, P < 0.05; 1 v 3, P < 0.001). CONCLUSION: The inverse relation between the extent of inflammatory activity in plaque tissues of culprit lesions and the clinical stability of the ischaemic syndrome supports the concept that reduction of inflammation favours plaque stabilisation. At the same time, the considerable overlap between groups indicates that patients with clinically stable angina do not all have histologically stable plaques.

Angina Pectoris↗