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1.
Sci Rep ; 10(1): 12257, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32704130

RESUMO

Diagnosing stable ischemic heart disease (IHD) is challenging, especially in females. Currently, no blood test is available. Plasma extracellular vesicles (EV) are emerging as potential biomarker source. We therefore aimed to identify stress induced ischemia due to stable IHD with plasma extracellular vesicle protein levels in chest pain patients. We analyzed 450 patients suspected for stable IHD who were referred for 82Rb PET/CT in the outpatient clinic. Blood samples were collected before PET/CT and plasma EVs were isolated in 3 plasma subfractions named: TEX, HDL, LDL. In total 6 proteins were quantified in each of these subfractions using immuno-bead assays. CD14 and CystatinC protein levels were independent significant predictors of stress-induced ischemia in the LDL and the HDL subfraction and SerpinC1 and SerpinG1 protein levels in the HDL fraction. Subgroup-analysis on sex revealed that these associations were completely attributed to the associations in women. None of the significant EV proteins remained significant in men. Plasma EV proteins levels are associated with the presence of stable IHD in females presenting with chest pain. This finding, if confirmed in larger cohort studies could be a crucial step in improving diagnostic assessment of women with suspected IHD.


Assuntos
Dor no Peito/etiologia , Dor no Peito/metabolismo , Vesículas Extracelulares/metabolismo , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/metabolismo , Proteínas/metabolismo , Estresse Fisiológico , Idoso , Biomarcadores , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Proteoma , Proteômica/métodos , Fatores de Risco , Fatores Sexuais
2.
Atherosclerosis ; 231(2): 346-51, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24267249

RESUMO

OBJECTIVE: Atherosclerosis is associated with increased levels of plasma cytokines and expression of Toll-like receptors (TLRs). Yet, little is known about the potential use of TLR ligand induced cytokine release as a biomarker of coronary artery disease (CAD). In this study, we investigated whether TLR ligand induced cytokine release is associated with atherosclerotic disease severity and its predictive value for future cardiovascular events. METHODS: Blood samples were obtained from 260 patients with stable angina and 15 healthy controls. Cytokine levels of TNFα, IL-8 and IL-6 were measured after 2 h of whole blood stimulation with 10 ng/ml lipopolysaccharide (LPS, TLR4 ligand) and P3C 500 ng/ml (TLR2 ligand). In a subgroup, dose-response curves were created using additional LPS concentrations. RESULTS: LPS induced whole blood release of TNFα and IL-6, but not IL-8, was significantly higher in patients compared to healthy controls. Among CAD patients, TLR responses did hardly differ when associated with the presence of traditional risk factors and atherosclerotic disease severity (number of diseased vessels and coronary stenosis degree). Patients with secondary events during follow-up showed a trend towards an increased TLR response. Furthermore, positive associations were found between CRP levels and TLR-induced TNFα (CRP<2: 2055 pg/ml; CRP>2: 2364 pg/ml) and IL-6 production (CRP<2: 1742 pg/ml; CRP>2: 2250 pg/ml). CONCLUSION: In conclusion, TLR-induced whole blood cytokine release in patients with stable angina indicates the presence of coronary atherosclerosis but does not reflect its severity.


Assuntos
Angina Estável/sangue , Doença da Artéria Coronariana/sangue , Citocinas/metabolismo , Leucócitos/citologia , Lipopolissacarídeos/sangue , Receptores Toll-Like/sangue , Idoso , Área Sob a Curva , Aterosclerose , Proteína C-Reativa/metabolismo , Antígeno CD11b/metabolismo , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Selectina-P/metabolismo , Fatores de Risco
3.
Neth Heart J ; 21(10): 467-71, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23975618

RESUMO

Cardiovascular disease is a major public health problem worldwide. Its growing burden is particularly ominous in Asia, due to increasing rates of major risk factors such as diabetes, obesity and smoking. There is an urgent need for early identification and treatment of individuals at risk of adverse cardiovascular events. Plasma extracellular vesicle proteins are novel biomarkers that have been shown to be useful in the diagnosis, risk stratification and prognostication of patients with cardiovascular disease. Ongoing parallel biobank initiatives in European (the Netherlands) and Asian (Singapore) populations offer a unique opportunity to validate these biomarkers in diverse ethnic groups.

4.
Eur Surg Res ; 45(1): 34-40, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20720431

RESUMO

OBJECTIVE: Elective repair of abdominal aortic aneurysms (AAA) is associated with significant morbidity and mortality. Large amounts of AAA tissue are necessary to assess heterogeneity among AAA and to correct for potential confounders such as known risk factors. The Aneurysm-express study aims to identify different types of AAA using inflammatory markers in the aneurysm wall that predict postoperative cardiovascular adverse events and mortality, therefore allowing individual risk assessment. METHODS: The Aneurysm-express is an ongoing prospective cohort study including AAA patients undergoing open repair. At baseline, blood is drawn, relevant clinical data are collected and the standard diagnostic modalities are performed. During surgery a specimen of the ventral AAA wall is collected and processed to study protein expressions and histology. INTERIM RESULTS: The study commenced in 2003 in 2 medical centers and currently holds information and material of >300 AAA patients, making it the largest reported aneurysm biobank. Patients are followed for 3 years after surgery for occurring cardiovascular events. The current mean follow-up is 2.1 ± 1.3 years with an event rate of 27%. CONCLUSION: The large amount of structurally stored tissue and blood combined with clinical characteristics and follow-up provide an excellent soil for indepth pathophysiological analyses, with assessment of AAA heterogeneity in combination with postoperative clinical outcome.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Idoso , Aorta Torácica/cirurgia , Aneurisma da Aorta Abdominal/classificação , Implante de Prótese Vascular/métodos , Estudos de Coortes , Doença da Artéria Coronariana/complicações , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores de Tempo , Resultado do Tratamento
5.
Heart ; 94(6): 770-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17686802

RESUMO

BACKGROUND: Toll-like receptors (TLRs) are key players in innate immunity and are causally related to arterial occlusive disease and arterial remodelling. The release of proinflammatory cytokines following TLR ligand binding is increased in patients with unstable angina. OBJECTIVE: To examine the effect of a percutaneous coronary intervention (PCI) on TLR2 and TLR4 response and expression. METHODS: In 70 PCI patients, blood samples were gathered after sheath insertion and 2 hours after the catheterisation. TLR2 and TLR4 expression on, and tumour necrosis factor alpha (TNFalpha) levels in, monocytes were measured with flow cytometry. Whole blood was stimulated overnight with the TLR2 ligand Pam3Cys and the TLR4 ligand lipopolysaccharide. TNFalpha was determined in the stimulated samples and considered to be a measure of the TLR response. Baseline TLR expression and response were studied in relation to angiographic luminal stenosis and fractional flow reserve (FFR) measurement. RESULTS: A significant relation was found between TLR response and the angiographic percentage diameter stenosis, number of diseased vessels and FFR outcome. Furthermore, 2 hours after PCI a significant decrease in TLR2 and TLR4 response (p<0.001) and TLR2 and TLR4 expression (p = 0.001 and p = 0.068, respectively) was seen. CONCLUSION: TLR response is positively associated with percentage diameter stenosis, multivessel disease and FFR outcome. Systemic TLR2 and TLR4 response and expression decrease after PCI. These results suggests that the TLR signalling pathway encompasses a potential biomarker for myocardial ischaemia in stable coronary artery disease.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Angina Instável/sangue , Arteriopatias Oclusivas/sangue , Doença da Artéria Coronariana/sangue , Receptor 2 Toll-Like/sangue , Receptor 4 Toll-Like/sangue , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Angina Instável/fisiopatologia , Arteriopatias Oclusivas/fisiopatologia , Angiografia Coronária , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Estenose Coronária/fisiopatologia , Feminino , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptor 2 Toll-Like/fisiologia , Receptor 4 Toll-Like/fisiologia , Fator de Necrose Tumoral alfa/sangue
6.
Atherosclerosis ; 197(1): 95-104, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17888930

RESUMO

BACKGROUND: Toll like receptors (TLR) have been recognized for their role in atherosclerotic lesion development and progression. Endogenous TLR ligands that are also expressed in atherosclerotic tissues have been shown to promote atherosclerosis in mice. Since repetitive stimulation of TLR induces an attenuated inflammatory response, we hypothesized that the TLR response is altered during atherosclerosis development, due to chronic exposure to endogenous ligands. METHODS AND RESULTS: We examined five groups of both ApoE-/- and C57Bl/6 mice aged 5, 10, 15, 25 and 40 weeks. In ApoE-/- mice with advanced stages of atherosclerosis, levels of mRNA encoding TLR2 and TLR4, the endogenous TLR ligands EDA and hsp60 as well as intracellular TLR-regulating mediators, like IRAK-M, were increased. Systemic TLR cell surface expression on circulating monocytes and EDA plasma levels were significantly increased in ApoE-/- mice with advanced atherosclerosis. We also observed that the endogenous TLR ligand EDA was capable of activating the TLR-signaling pathway in white blood cells. During the plaque progression stage however, stimulation of TLR2 and TLR4 in blood samples attenuated MIP-1 alpha and RANTES release in atherosclerotic mice. CONCLUSION: During atherosclerotic lesion development, TLR2 and TLR4 expression increases in atherosclerotic plaques and on circulating blood cells. However, with advanced stages of atherosclerotic disease, circulating blood cells become less responsive to TLR ligation, which may be due to chronic TLR engagement by endogenous EDA.


Assuntos
Aterosclerose/metabolismo , Aterosclerose/patologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Aorta Torácica/fisiologia , Apolipoproteínas E/genética , Aterosclerose/imunologia , Progressão da Doença , Fibronectinas/sangue , Fibronectinas/química , Expressão Gênica/imunologia , Ligantes , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Monócitos/metabolismo , Estrutura Terciária de Proteína , RNA Mensageiro/metabolismo , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Vasculite/imunologia , Vasculite/metabolismo , Vasculite/patologia
7.
Stroke ; 36(8): 1735-40, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16002764

RESUMO

BACKGROUND AND PURPOSE: During carotid endarterectomy (CEA), microemboli may occur, resulting in perioperative adverse cerebral events. The objective of the present study was to investigate the relation between atherosclerotic plaque characteristics and the occurrence of microemboli or adverse events during CEA. METHODS: Patients (n=200, 205 procedures) eligible for CEA were monitored by perioperative transcranial Doppler. The following phases were discriminated during CEA: dissection, shunting, release of the clamp, and wound closure. Each carotid plaque was stained for collagen, macrophages, smooth muscle cells, hematoxylin, and elastin. Semiquantitative analyses were performed on all stainings. Plaques were categorized into 3 groups based on overall appearance (fibrous, fibroatheromatous, or atheromatous). RESULTS: Fibrous plaques were associated with the occurrence of more microemboli during clamp release and wound closure compared with atheromatous plaques (P=0.04 and P=0.02, respectively). Transient ischemic attacks and minor stroke occurred in 5 of 205 (2.4%) and 6 of 205 (2.9%) patients, respectively. Adverse cerebral outcome was significantly related to the number of microembolic events during dissection (P=0.003) but not during shunting, clamp release, or wound closure. More cerebrovascular adverse events occurred in patients with atheromatous plaques (7/69) compared with patients with fibrous or fibroatheromatous plaques (4/138) (P=0.04). CONCLUSIONS: Intraoperatively, a higher number of microemboli were associated with the presence of a fibrous but not an atheromatous plaque. However, atheromatous plaques were more prevalent in patients with subsequent immediate adverse events. In addition, specifically the number of microemboli detected during the dissection phase were related to immediate adverse events.


Assuntos
Aterosclerose/diagnóstico , Artérias Carótidas/patologia , Estenose das Carótidas/patologia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Endarterectomia das Carótidas/métodos , Ultrassonografia Doppler Transcraniana/métodos , Adulto , Idoso , Trombose das Artérias Carótidas/patologia , Colágeno/química , Elastina/metabolismo , Eletroencefalografia , Feminino , Hematoxilina/metabolismo , Humanos , Inflamação , Isquemia , Macrófagos/metabolismo , Imageamento por Ressonância Magnética , Masculino , Microcirculação/patologia , Pessoa de Meia-Idade , Músculo Liso/citologia , Fenótipo , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia , Cicatrização
8.
Cardiovasc Res ; 66(1): 162-9, 2005 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15769459

RESUMO

BACKGROUND: Toll like receptors (Tlr) are essential in activation of the innate immune system. We recently described that peptidoglycan, an exogenous Tlr2 specific ligand, is present in human atherosclerotic plaques and associated with histological markers for plaque vulnerability. Also, endogenous Tlr2 ligands can be expressed in atherosclerotic tissues. Here, we determined whether Tlr2 stimulation promotes pro-inflammatory cytokine/chemokine production in vitro and augments neointima formation and development of atherosclerotic plaques in vivo. METHODS AND RESULTS: We detected Tlr2 using Western blot and RT-PCR in human coronary arteries and primary adventitial fibroblasts. RNAse protection assay demonstrated significant induction of IL-1, IL-6, IL-8 and MCP-1 mRNA after Tlr2 stimulation in human adventitial fibroblasts in vitro. ELISA demonstrated induction of IL-6, IL-8 and MCP-1. In vivo application of Pam(3)Cys-SK(4), a synthetic Tlr2 ligand, on femoral arteries of C57BL/6 wild type (WT) mice using a peri-adventitial cuff, significantly enhanced neointima formation compared to control arteries. This increased inflammatory response was not observed in Tlr2 knockout (Tlr2-/-) mice. In ApoE knockout mice (ApoE-/-), application of the same Tlr2 ligand led to a significant increase in atherosclerotic plaque development. CONCLUSION: Local arterial Tlr2 stimulation induced neointima and atherosclerotic plaque formation in mouse femoral arteries. Tlr2 stimulation may be an important mediator in arterial occlusive disease.


Assuntos
Doença da Artéria Coronariana/imunologia , Glicoproteínas de Membrana/metabolismo , Receptores de Superfície Celular/metabolismo , Túnica Íntima/efeitos dos fármacos , Animais , Apolipoproteínas E/genética , Western Blotting/métodos , Quimiocina CCL2/análise , Quimiocina CCL2/genética , Fibroblastos/imunologia , Humanos , Interleucina-1/análise , Interleucina-1/genética , Interleucina-6/análise , Interleucina-6/genética , Interleucina-8/análise , Interleucina-8/genética , Ligantes , Lipoproteínas/farmacologia , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Patológica/induzido quimicamente , RNA Mensageiro/análise , Receptores de Superfície Celular/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 2 Toll-Like , Receptores Toll-Like , Túnica Íntima/patologia
9.
J Am Coll Cardiol ; 38(3): 718-23, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11527623

RESUMO

OBJECTIVES: This study was designed to determine whether arterial remodeling and plaque vulnerability are influenced by systemic factors. BACKGROUND: Atherosclerotic luminal narrowing is caused by gradual plaque growth and arterial remodeling. In the acute phase, luminal narrowing may be accelerated by acute thrombus formation, usually precipitated by rupture of a vulnerable plaque. METHODS: Femoral arteries were obtained from elderly individuals at autopsy. Pairs of atherosclerotic femoral arteries from 42 individuals were examined. The arteries were divided in 1-cm intervals. Plaque size, the mode of arterial remodeling and histopathologic characteristics of plaque vulnerability (lipid-rich core and plaque inflammation) were compared between right and left femoral arteries obtained from the same individual. A role for systemic factors was assumed if a phenomenon was equally present in both arteries. RESULTS: There was concordance in average plaque size (r(2) = 0.5, p < 0.001), expansive remodeling (kappa = 0.42, p = 0.007) and occurrence of plaques containing a large lipid-rich core (kappa = 0.60, p = 0.001), but no concordance in plaque inflammation (kappa = 0.067, p = 0.61) between right and left arteries. CONCLUSIONS: These results suggest that not only the amount of atherosclerosis, but also arterial remodeling and lipid deposition in plaques, are influenced by systemic factors. The nonhomogeneous distribution of inflammation in atherosclerotic arteries supports the hypothesis that plaque inflammation is locally affected.


Assuntos
Arteriosclerose/patologia , Endotélio Vascular/patologia , Artéria Femoral/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Artéria Femoral/química , Humanos , Lipídeos/análise , Masculino
10.
FEBS Lett ; 501(1): 37-41, 2001 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-11457452

RESUMO

Matrix metalloproteinase (MMP) activation is an essential feature of pathological and physiological arterial enlargement or shrinkage. Recently, furin-activated membrane type-1 MMP (MT1-MMP) was identified as the in vivo activator of MMP2 in mice. Although arterial enlargement and shrinkage are important in several pathological processes, this proprotein convertase-MT1-MMP axis has not been described during arterial remodeling. In rabbit femoral and carotid arteries, we report an increase in furin and MT1-MMP mRNA levels before and at the onset of arterial remodeling followed by an increase in activated MMP2. This reveals the presence of the proprotein convertase-MT1-MMP axis in flow-induced arterial remodeling and identifies furin as a possible target for local intervention in pathological arterial remodeling.


Assuntos
Artérias Carótidas/enzimologia , Artérias Carótidas/fisiologia , Artéria Femoral/enzimologia , Artéria Femoral/fisiologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloendopeptidases/genética , Subtilisinas/genética , Animais , Derivação Arteriovenosa Cirúrgica , Artérias Carótidas/citologia , Artérias Carótidas/cirurgia , Ativação Enzimática , Indução Enzimática , Artéria Femoral/citologia , Artéria Femoral/cirurgia , Furina , Imuno-Histoquímica , Ligadura , Metaloproteinases da Matriz Associadas à Membrana , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coelhos , Fluxo Sanguíneo Regional
11.
Atherosclerosis ; 157(1): 117-22, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11427210

RESUMO

The presence of Chlamydia pneumoniae in the human arterial system has mainly been determined in atherosclerotic plaque, whereas the adventitia has remained relatively unexplored. We assessed the presence of C. pneumoniae in all three vessel wall layers of coronary (n=72) and brachial (n=48) arteries in relation to local atherosclerosis. Immunohistochemical staining of C. pneumoniae was observed in plaque and adventitia. Cells stained for C. pneumoniae were detected in the same areas as cells stained for macrophages in adjacent sections. C. pneumoniae staining in the adventitia was associated with the extent and severity of atherosclerosis. Coronary sections with C. pneumoniae staining in both adventitia and plaque more often contained advanced atherosclerosis than sections with staining only in the adventitia. Staining was observed more often in the coronary artery than in the brachial artery (24/72 vs. 5/48 and 51/72 vs. 8/48 for plaque and adventitia, respectively, P=0.004 and P<0.001). PCR confirmed the presence of C. pneumoniae DNA in the adventitia. In summary, the adventitia of atherosclerotic coronary arteries frequently contains C. pneumoniae that seems to be located within macrophages. These results might indicate a possible route for infected circulating macrophages to home into atherosclerotic lesions in the artery via vasa vasorum.


Assuntos
Chlamydophila pneumoniae/isolamento & purificação , Doença da Artéria Coronariana/microbiologia , Idoso , Idoso de 80 Anos ou mais , Infecções por Chlamydophila/complicações , Infecções por Chlamydophila/patologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Túnica Íntima/microbiologia , Túnica Íntima/patologia , Túnica Média/microbiologia , Túnica Média/patologia
12.
Circulation ; 103(12): 1613-7, 2001 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-11273986

RESUMO

BACKGROUND: Chlamydia pneumoniae has been suggested to play a role in the origin of atherosclerosis. We studied the prevalence of C pneumoniae at multiple locations in the arterial system within the same individual. Studying the association between atherosclerosis and C pneumoniae within the individual excludes confounding by interindividual variability. METHODS AND RESULTS: Postmortem, the presence in the intima/plaque and media of C pneumoniae membrane protein was determined by use of a C pneumoniae-specific monoclonal antibody. In 24 individuals, 33 arterial locations were studied (n=738 segments). Area stenosis was determined in adjacent cross sections. In all individuals, immunostaining of C pneumoniae was observed in >/=1 artery. The highest prevalences were observed in the abdominal aorta (67%), internal and common iliac arteries (41%), and coronary arteries (33%). The lowest prevalences were observed in the radial (0%) and cerebral (2%) arteries. Within the individual, area stenosis was larger in cross sections with immunoreactivity compared with cross sections without immunoreactivity (31.0+/-11.9% versus 14.3+/-6.1%, respectively; P:<0.001). In the individual, immunoreactivity was observed in 15+/-10% of the arteries (range, 3% to 45%). Between individuals, the percentage of arteries with immunoreactivity to C pneumoniae was associated with the average area stenosis throughout the arterial system (r(2)=0.56, P:<0.001). CONCLUSIONS: C pneumoniae was mostly observed at locations that are related to clinically relevant features. Within the individual, the distribution of C pneumoniae is associated with the distribution of atherosclerosis. The role of the microorganism in atherosclerotic disease remains to be elucidated.


Assuntos
Artérias/microbiologia , Arteriosclerose/microbiologia , Infecções por Chlamydophila/microbiologia , Chlamydophila pneumoniae/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Artérias/patologia , Arteriosclerose/epidemiologia , Arteriosclerose/patologia , Infecções por Chlamydophila/epidemiologia , Infecções por Chlamydophila/patologia , Comorbidade , Constrição Patológica/microbiologia , Constrição Patológica/patologia , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Túnica Média/microbiologia , Túnica Média/patologia
13.
Atherosclerosis ; 150(2): 245-53, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10856516

RESUMO

Atherosclerotic luminal narrowing is determined by plaque mass and the mode of geometrical remodeling. Recently, we reported that the type of atherosclerotic remodeling is associated with the presence of histological markers for plaque vulnerability. Inflammation and matrix degrading proteases (MMPs) may play a role in both plaque vulnerability and in expansive arterial remodeling. The aim of the present study was to investigate the association between the remodeling mode and the localization of macrophages and MMPs in coronary atherosclerotic segments. From 36 atherosclerotic coronary arteries, 45 and 51 segments were selected with a vessel area that was >10% smaller and larger compared with the adjacent segments, respectively. No significant difference in staining for macrophages was observed between segments with expansive and constrictive remodeling. More MMP-2 and MMP-9 staining was observed in plaques of expansively remodeled segments compared with constrictively remodeled segments. In general, MMP-staining was less evident in the adventitial layer compared with the plaque. Zymography revealed more active MMP-2 in expansively remodeled segments compared with constrictively remodeled segments (340+/-319 vs. 199+/-181 (adjusted counts/mm(2)), respectively, P=0.019). Zymography did not show differences in inactive MMP-2 or MMP-9 among groups. It might be postulated that MMPs within the plaque play a causal role not only in plaque vulnerability but also in de novo atherosclerotic remodeling.


Assuntos
Doença da Artéria Coronariana/enzimologia , Vasos Coronários/enzimologia , Macrófagos/patologia , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Idoso , Anticorpos Monoclonais , Biomarcadores , Cadáver , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Progressão da Doença , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Metaloproteinase 1 da Matriz/imunologia , Metaloproteinase 2 da Matriz/imunologia , Metaloproteinase 9 da Matriz/imunologia
14.
Phys Med Biol ; 45(6): 1465-75, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10870704

RESUMO

Intravascular ultrasound elastography is a method for measuring the local elastic properties using intravascular ultrasound (IVUS). The elastic properties of the different tissues within the atherosclerotic plaque are measured through the strain. Knowledge of these elastic properties is useful for guiding interventional procedures (balloon dilatation, ablation) and detection of the vulnerable plaque. In the last decade, several groups have applied elastography intravascularly with various levels of success. In this paper, the approaches of the different research groups will be discussed. The focus will be on our approach to the application of intravascular elastography. Elastograms were acquired in vitro and in vivo using the relative local displacements between IVUS images acquired at two levels of intravascular pressure with a 30 MHz mechanical or a 20 MHz array echo catheter. These displacements were estimated from the time shift between gated radiofrequency echo signals using cross-correlation algorithms with interpolation around the peak. Experiments on gel-based phantoms mimicking atherosclerotic vessels demonstrated the capability of elastography to identify soft and hard tissues independently of the echogenicity contrast. In vitro experiments on human arteries have demonstrated the potential of intravascular elastography to identify different plaque types based on their mechanical properties. These plaques could not be identified using the IVUS image alone. In vivo experiments revealed that reproducible elastograms could be obtained near end-diastole. Partial validation using the echogram was performed. Intravascular elastography provides information that is frequently unavailable or inconclusive from the IVUS image and which may therefore assist in the diagnosis and treatment of atherosclerotic disease.


Assuntos
Arteriosclerose/diagnóstico por imagem , Ultrassonografia/métodos , Arteriosclerose/diagnóstico , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Elasticidade , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/patologia , Humanos , Imagens de Fantasmas , Ultrassonografia/instrumentação
15.
Arterioscler Thromb Vasc Biol ; 19(1): 54-8, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9888866

RESUMO

-Retrospectively, plaque rupture is often colocalized with inflammation of the cap and shoulder of the atherosclerotic plaque. Local inflammation is therefore considered a potential marker for plaque vulnerability. However, high specificity of inflammation for plaque rupture is a requisite for application of inflammation markers to detect rupture-prone lesions. The objective of the present study was to investigate the prevalence and distribution (local versus general) of inflammatory cells in nonruptured atherosclerotic plaques. The cap and shoulder of the plaque were stained for the presence of macrophages and T lymphocytes in 282 and 262 cross sections obtained from 74 coronary and 50 femoral arteries, respectively. From most cases, 2 atherosclerotic arteries were studied to gain insight into the local and systemic distribution of the inflammatory process. In 45% and 41% of all cross sections, staining for macrophages was observed in the femoral and coronary arteries, respectively. Rupture of the fibrous cap was observed in 2 femoral and 3 coronary artery segments and was always colocalized with inflammatory cells. At least 1 cross section stained positively for CD68 or acid phosphatase in 84% and 71% of all femoral and coronary arteries, respectively. Only 1 femoral and 6 coronary arteries revealed a positive stain for CD68 in all investigated segments. Inflammation of the cap and shoulder of the plaque is a common feature, locally observed, in atherosclerotic femoral and coronary arteries. The high prevalence of local inflammatory responses should be considered if they are used as a diagnostic target to detect vulnerable, rupture-prone lesions.


Assuntos
Arteriosclerose/patologia , Arterite/patologia , Doença da Artéria Coronariana/patologia , Artéria Femoral/patologia , Fosfatase Ácida/análise , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Feminino , Humanos , Imuno-Histoquímica , Antígenos Comuns de Leucócito/análise , Macrófagos/química , Macrófagos/patologia , Masculino , Ruptura Espontânea
16.
J Am Coll Cardiol ; 32(3): 655-62, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9741507

RESUMO

OBJECTIVE: To relate local arterial geometry with markers that are thought to be related to plaque rupture. BACKGROUND: Plaque rupture often occurs at sites with minor luminal stenosis and has retrospectively been characterized by colocalization of inflammatory cells. Recent studies have demonstrated that luminal narrowing is related with the mode of atherosclerotic arterial remodeling. METHODS: We obtained 1,521 cross section slices at regular intervals from 50 atherosclerotic femoral arteries. Per artery, the slices with the largest and smallest lumen area, vessel area and plaque area were selected for staining on the presence of macrophages (CD68), T-lymphocytes (CD45RO), smooth muscle cells (alpha-actin) and collagen. RESULTS: Inflammation of the cap or shoulder of the plaque was observed in 33% of all cross sections. Significantly more CD68 and CD45RO positive cells, more atheroma, less collagen and less alpha-actin positive staining was observed in cross sections with the largest plaque area and largest vessel area vs. cross sections with the smallest plaque area and smallest vessel area, respectively. No difference in the number of inflammatory cells was observed between cross sections with the largest and smallest lumen area. CONCLUSION: Intraindividually, pathohistologic markers previously reported to be related to plaque vulnerability were associated with a larger plaque area and vessel area. In addition, inflammation of the cap and shoulder of the plaque was a common finding in the atherosclerotic femoral artery.


Assuntos
Actinas/metabolismo , Arteriosclerose/patologia , Arterite/patologia , Colágeno/metabolismo , Artéria Femoral/patologia , Macrófagos/patologia , Linfócitos T/patologia , Idoso , Idoso de 80 Anos ou mais , Arteriosclerose/imunologia , Arterite/imunologia , Feminino , Artéria Femoral/imunologia , Humanos , Processamento de Imagem Assistida por Computador , Técnicas Imunoenzimáticas , Macrófagos/imunologia , Masculino , Linfócitos T/imunologia , Grau de Desobstrução Vascular/fisiologia
17.
Atherosclerosis ; 137(1): 205-10, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9568753

RESUMO

The atherosclerotic carotid artery is easily accessible for non-invasive duplex investigation. The aim of the present post mortem study was to examine whether plaque accumulation and luminal stenosis in the common carotid artery is representative for atherosclerotic plaque accumulation and luminal stenosis in other peripheral arteries. A total of 3765 cross-sections were obtained at regular intervals from 240 arteries (24 individuals). Five types of peripheral arteries were investigated: common carotid, femoral, common iliac, external iliac and renal arteries. In each cross-section, the lumen area, vessel area, plaque area and maximal plaque thickness was measured. For each location, the percentage luminal stenosis and relative plaque area was calculated. Relative plaque area was defined as the percentage of the vessel area which was occupied by plaque. Weak correlations (r=0.41-0.59) were observed between percentage relative plaque area or maximal plaque thickness in the common carotid artery and percentage relative plaque area in other peripheral arteries. Neither plaque accumulation nor luminal stenosis in the common carotid artery correlated with the percentage luminal stenosis in other peripheral arteries (P > 0.05). We conclude that plaque area in the common carotid artery is weakly correlated with plaque area and not correlated with luminal stenosis in other peripheral arteries.


Assuntos
Artérias/patologia , Arteriosclerose/patologia , Artéria Carótida Primitiva/patologia , Estenose das Carótidas/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Interpretação Estatística de Dados , Feminino , Artéria Femoral/patologia , Humanos , Artéria Ilíaca/patologia , Masculino , Microtomia , Mudanças Depois da Morte , Artéria Renal/patologia , Túnica Íntima/patologia , Túnica Média/patologia
18.
Arterioscler Thromb Vasc Biol ; 17(11): 2617-21, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9409234

RESUMO

Arteries may demonstrate compensatory enlargement in response to plaque accumulation. It has been proposed that enlargement is achieved by the expansion of the nondiseased (plaque-free) vessel wall. In this study, we assessed this hypothesis. Post mortem, 32 atherosclerotic coronary arteries (left anterior descending, n = 10; left circumflex, n = 11; and right coronary, n = 11) and 54 atherosclerotic femoral arteries were pressure fixed. Cross sections (coronary arteries, n = 537; femoral arteries, n = 1602) were obtained for analysis every 2.5 mm for the coronary arteries and every 5.0 mm for the femoral arteries. From these cross sections, we determined the degree of remodeling and an eccentricity index. Finally, we measured the extent of plaque-free vessel wall. The plaque-free vessel wall was defined as (1) no plaque present or (2) plaque thickness < 0.5 mm. A very weak, negative correlation was observed between the degree of remodeling and the extent of the plaque-free vessel wall (coronary arteries: no plaque r2 = .13, P < .01; < 0.5 mm plaque r2 = .15, P < .05; femoral arteries: no plaque r2 = .02, P < .01; < 0.5 mm plaque r2 = 0.04, P < .01). The degree of remodeling did not correlate with the eccentricity index (coronary arteries r2 = .002, P > .05 and femoral arteries r2 = .001, P > .05). Thus, compensatory enlarged segments did not reveal a larger circumference of plaque-free vessel wall compared with segments that failed to enlarge. This study provides no support for the hypothesis that nondiseased vessel-wall expansion is responsible for compensatory enlargement in atherosclerotic arteries.


Assuntos
Arteriosclerose/patologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Artéria Femoral/patologia , Idoso , Idoso de 80 Anos ou mais , Antropometria , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Arterioscler Thromb Vasc Biol ; 17(11): 3057-63, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9409293

RESUMO

Luminal stenosis can be based on large atherosclerotic plaques in compensatory enlarged segments or on relatively little plaques in shrunken segments. In the present study, the contribution of plaque formation and remodeling to luminal narrowing was compared among six types of arteries prone to symptomatic atherosclerosis. Cross-sections (n = 5195) were obtained at regular intervals from 329 arteries. For each artery, the cross-section that contained the least amount of plaque was considered to be the reference. For each cross-section, the percentage of lumen area decrease was expressed as a percentage of the lumen area at the reference site (luminal stenosis). Similarly, the area encompassed by the internal elastic lamina (IEL area) was expressed as a percentage of the IEL area at the reference site (relative IEL area). All cross-sections were categorized in three groups: relative IEL area > 105% (enlargement), 95% to 105% (no remodeling), and < 95% (shrinkage). The prevalence of enlargement (50% to 75%) was significantly higher compared with shrinkage (8% to 25%). Shrinkage was observed most frequently in the femoral arteries (25%) and infrequently in the renal arteries (8%). For all types of arteries, the relative IEL area correlated negatively with luminal stenosis (P < .001). Regression analysis of relative IEL area on luminal stenosis, however, showed significant differences in the first-order regression coefficients among artery types. On average, plaque increase was more compensated for by enlargement in the coronary, common carotid, and renal arteries compared with the arteries obtained from the lower extremities. Anatomic regional differences were observed in the impact of arterial wall remodeling on percent luminal stenosis in de novo atherosclerotic lesions.


Assuntos
Artérias/patologia , Arteriosclerose/patologia , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Primitiva/patologia , Estenose das Carótidas/patologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Feminino , Artéria Femoral/patologia , Humanos , Artéria Ilíaca/patologia , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Artéria Renal/patologia
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