RESUMEN
Multiple reports have demonstrated an association between Chlamydia pneumoniae (Cpn) and cardiovascular disease. In this study we evaluated the effect of Cpn infections on early lesion progression in C57BL/6J mice. Since plaque formation in these mice does not develop past the initial stage, we thought these mice might be a better model for unravelling the effect of Cpn infection on early lesion type progression. C57BL/6J mice were fed an atherogenic diet and injected 10 times with 5 x 10(7) IFU Cpn or mock. At sacrifice, lesion number, size and type were analysed. To study the role of Cpn in inflammation, serum amyloid P (SAP) in plasma was determined as well as T-cells, macrophages and SAP in the lesions. In the aortic sinus of both groups, type 2 lesions were found. Cpn infection resulted in a 2.2-fold increase in total lesion size (Cpn: 10821+/-2429 microm(2)vs mock: 5022+/-1348 microm(2); p=0.04). No difference in lesion number was observed. Also, Cpn infection increased SAP in the lesions from 1.10(-4)+/-0.1.10(-4) SAP-positive cells/lesion area to 10.10(-4)+/-1.10(-4) SAP-positive cells/lesion area (p=0.05). The influx of T-lymphocytes and macrophages in the lesions as well as SAP plasma levels were not different between groups. Multiple Cpn infections resulted in a significant increase in total lesion size of C57BL/6J mice. Increase in total SAP-positive area in infected mice suggests a role for this acute-phase protein in lesion enlargement.
Asunto(s)
Aterosclerosis/microbiología , Infecciones por Chlamydophila/complicaciones , Chlamydophila pneumoniae/crecimiento & desarrollo , Componente Amiloide P Sérico/metabolismo , Animales , Aterosclerosis/sangre , Aterosclerosis/patología , Infecciones por Chlamydophila/sangre , Infecciones por Chlamydophila/microbiología , Infecciones por Chlamydophila/patología , Colesterol/sangre , ADN Bacteriano/química , ADN Bacteriano/genética , Histocitoquímica , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa , Seno Aórtico/inmunología , Seno Aórtico/microbiología , Seno Aórtico/patología , Organismos Libres de Patógenos Específicos , Linfocitos T/patología , Triglicéridos/sangreRESUMEN
OBJECTIVES: To study whether Chlamydia pneumoniae (Cpn) infection affects atherosclerotic plaque morphology in atherogenic (LDLr/ApoE(-/-)) mice. METHODS: In mice sacrificed 20 or 40 weeks after Cpn infection aortic arch sections were analysed for lesion and fibrous cap area and the presence of matrix metalloproteinases (MMP)-2 and -9. RESULTS: All infected mice seroconverted, demonstrated Cpn DNA in their aortas on PCR and developed atherosclerotic plaques. Infection was not associated with changes in lesion area or type, but was associated with reduced the fibrous cap area and increased MMP-2 and -9 immunoreactivity. CONCLUSION: These findings suggest that Cpn infection may predispose to plaque instability.
Asunto(s)
Arteriosclerosis/microbiología , Infecciones por Chlamydophila/complicaciones , Chlamydophila pneumoniae , Actinas/análisis , Animales , Anticuerpos Antibacterianos/análisis , Aorta/metabolismo , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/microbiología , Enfermedades de la Aorta/patología , Apolipoproteínas E/genética , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Chlamydophila pneumoniae/aislamiento & purificación , ADN Bacteriano/análisis , Inmunohistoquímica , Masculino , Metaloproteinasa 2 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/análisis , Ratones , Ratones Noqueados , Fenotipo , Receptores de LDL/genéticaRESUMEN
OBJECTIVE: Atherosclerosis is an inflammatory process and is characterised by the presence of T-lymphocytes in the lesions. To study the role of Chlamydophila pneumoniae (C. pneumoniae) in this process and the effect of infection on T-cell influx, we infected Apo E3-Leiden mice with C. pneumoniae and investigated the effect on lesion development and T-cell influx in atherosclerotic lesions at different time points post infection (pi). METHODS: Nine week old mice, fed an atherogenic diet, were either mock-infected or infected with C. pneumoniae and sacrificed at 1, 6 and 9 months pi. Longitudinal sections of the aortic arches of the mice were stained with hematoxylin-eosin for atherosclerotic lesion type and lesion area analysis, or with rabbit-anti-CD3(+) to detect the presence of T-cells in the atherosclerotic lesions. T-cell influx was expressed as number of T-lymphocytes/lesion area. RESULTS: At 1 month pi, type 1, 2 and 3 lesions were present. At other time points pi, more complex lesion types 4, 5a and 5b were also present. Although infection did not influence the total lesion number or area, we observed an effect of C. pneumoniae infection on lesion type. Infection resulted in a significant shift in lesion formation from type 3 to type 4 (P=0.022) at 6 months pi, and from type 4 to type 5a (P=0.002) at 9 months pi. T-cells were observed at every time point pi. At 1 month pi, a significant increase in T-cell influx in the C. pneumoniae-infected atherosclerotic lesions was observed (P=0.0005). CONCLUSION: This study shows that C. pneumoniae infection enhances the inflammatory process by increasing T-lymphocytes in the plaque and accelerates the formation of complex lesions.
Asunto(s)
Arteriosclerosis/microbiología , Infecciones por Chlamydia/complicaciones , Chlamydophila pneumoniae , Animales , Aortitis/inmunología , Aortitis/microbiología , Aortitis/patología , Arteriosclerosis/inmunología , Arteriosclerosis/patología , Colesterol/sangre , Dieta Aterogénica , Progresión de la Enfermedad , Femenino , Hipercolesterolemia/complicaciones , Masculino , Ratones , Ratones Endogámicos C57BL , Factores de Riesgo , Linfocitos T/patología , Triglicéridos/sangreRESUMEN
INTRODUCTION: As the mean age of haemodialysis patients is increasing, fewer patients will have suitable blood vessels for the creation of a Brescia-Cimino fistula and an increased use of graft implants is to be expected. METHODS: To assess the change in vascular access and the use of surveillance techniques, all haemodialysis centres in The Netherlands received a questionnaire regarding the types of vascular accesses and surveillance techniques used in their department on 31 December, 1996. The results were related to a comparable study done in 1987, shown between brackets. RESULTS: The response of the haemodialysis staff was 96%, of the vascular surgeons this was 91%. Sixty-two per cent (70%) of the patients had Brescia-Cimino fistulas, 21% (13%) Polytetrafluoroethylene (PTFE) graft fistulas, 17% (17%) other vascular accesses. Scheduled surveillance for stenosis detection was done by recirculation measurements in 6%, venous pressure measurements in 31%, Duplex scanning in 11% and angiography in 11% of the centres. When access problems occurred, 79% of the physicians performed recirculation measurements, 38% venous pressure measurements, 79% Duplex scanning and 100% angiography. In 46% of the centres PTA was done occasionally, and in 46% routinely for the treatment of stenotic complications in arteriovenous fistulas. CONCLUSIONS: The use of PTFE grafts and other types of vascular accesses has increased at the expense of BC fistulas. Recirculation and venous pressure measurements are primarily done when problems occur and not according to a standard surveillance schedule. For visualization of failing fistulas, 79% of the centres uses Duplex ultrasound analysis and 100% angiography. The popularity of PTA has increased from 46 to 92% of the centres.