Expression of adhesion molecules on endothelial cells stimulated byChlamydia pneumoniae

doi:10.1006/mpat.1996.0071

Microbial Pathogenesis

Volume 21, Issue 5, November 1996, Pages 407-411

https://doi.org/10.1006/mpat.1996.0071 Get rights and content

Abstract

Previous studies have shown thatC. pneumoniaeis able to infect human endothelial cellsin vitro. In this report, the ability ofC. pneumoniaeto induce the expression of E-selectin or endothelial-leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on human umbilical vein endothelial (HUVE) cell surface was investigated.C. pneumoniaewas found to cause a moderate upregulation of the adhesion molecules. Maximal expression of E-selectin was noted at 6 h post infection (p.i.) and that of ICAM-1 and VCAM-1 at 20 h p.i. The capability ofC. pneumoniaeto grow in endothelial cells and to stimulate the expression of adhesion molecules essential for leukocyte–endothelial cell interactions suggests a role forC. pneumoniaeas a local pathogenetic factor in vascular inflammatory alterations, including atherogenesis.

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Protective effects of ligustrazine on TNF-α-induced endothelial dysfunction
2012, European Journal of Pharmacology
Citation Excerpt :
Zhang et al. demonstrated a correlation between high levels of Hsp60 and the risk of coronary heart disease (CHD), which does not depend on conventional coronary heart disease risk factors (Zhang et al., 2010). HSP60 activates endothelial cells, smooth muscle cells and macrophages, induces the expression of cellular adhesion molecules, presents antigens to T cells and B cells, and generates autoantibodies and autoimmune response (Kol et al., 1999; Kaukoranta-Tolvanen, 1996; Yamazaki et al., 2004; Xu, 2002). Therefore, increased expression of ICAM-1 and HSP60 contributes to the pathogenesis of atherosclerosis.
To investigate the effects of Ligustrazine, a compound derived from chuanxiong, on tumor necrosis factor-α (TNF-α) stimulated endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α in vitro. Nitric oxide (NO) was measured as a standard of endothelial dysfunction. Two important indicators of autoimmunity, intracellular adhesion molecular-1 (ICAM-1) and heat shock protein 60 (HSP60), were selected to evaluate the influence of Ligustrazine on HUVECs. Ligustrazine (40 μg/ml) significantly reversed the decrease in NO production induced by TNF-α (5 ng/ml) in HUVECs. The expressions of ICAM-1 and HSP60 were increased by TNF-α treatment, but dramatically inhibited by treatment with ligustrazine in TNF-α-stimulated cells. Ligustrazine increased the production of NO in HUVECs and had an immunomodulatory effect on HUVECs stimulated with TNF-α by down-regulating the expression of ICAM-1 and HSP60. These results suggest that ligustrazine protects the endothelium via inhibition of immunological reactions, preventing atherosclerosis.
The effect of proatherogenic microbes on macrophage cholesterol homeostasis in apoE-deficient mice
2011, Microbial Pathogenesis
Citation Excerpt :
These hallmarks of endothelial dysfunction appear already at the early stages of atherogenesis. Both periodontitis [33,34] and C. pneumoniae [35] have been shown to increase the concentration of endothelial dysfunction markers in the circulation. We have previously shown that proatherogenic microbes infect the liver causing pro-inflammatory alterations and lipid disturbances [36].
Pathogens such as Aggregatibacter actinomycetemcomitans (Aa) and Chlamydia pneumoniae (Cpn) associate with an increased risk for cardiovascular diseases by inducing inflammation. We hypothesized that the pathogens affect the vascular wall by disturbing cholesterol homeostasis and endothelial function.
Aa- and Cpn-infections were induced in apoE-deficient mice by intravenous and intranasal applications, respectively. Cholesterol efflux from mouse peritoneal macrophages to apo(lipoprotein)A-I was assessed. The efflux capacity of mouse sera as acceptors of cholesterol from RAW264.7-macrophages was determined. Additionally, endothelial function was studied by following the relaxation capacity of rat mesenteric arteries after incubation in the conditioned culture media of the peritoneal macrophages isolated from the mice.
Infection increased serum phospholipid transfer protein (PLTP) and lipopolysaccharide (LPS) activity, as well as serum amyloid A (SAA) and TNF-α concentrations. Peritoneal macrophages of mice with Aa-infection showed increased cholesterol uptake and reduced cholesterol efflux. Sera of Cpn and Cpn + Aa-infected mice had reduced cholesterol efflux capacity from RAW264.7-macrophages. Conditioned macrophage medium from mice with chronic C. pneumoniae infection induced endothelial dysfunction. Additionally, concentrations of serum adhesion molecules, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in Cpn-groups and E-selectin in Cpn + Aa-group, were elevated. The serum markers of endothelial function correlated positively with SAA.
Aa- and Cpn-infections may generate proatherogenic changes in the vascular wall by affecting the macrophage cholesterol homeostasis and endothelial function.
Plaque Biology: Interesting Science or Pharmacological Treasure Trove?
2008, European Journal of Vascular and Endovascular Surgery
Citation Excerpt :
Certain infectious agents can evoke cellular and molecular changes supportive of a role in atherogenesis. Work has shown that chlamydial interaction with monocytes results in up-regulation of TNF-α and IL-β, both of which are associated with plaque development.49,50 Chlamydial production of HSP60 antigen activates human vascular endothelium, and increases TNF-α and MMP expression in macrophages.51
Our understanding of the events that occur within atherosclerotic plaques has improved dramatically over the last 2 decades, particularly with regard to the role of plaque destabilisation and the onset of clinical ischaemic syndromes. Many potential targets have been identified for therapeutic intervention aimed at disease prevention, plaque stabilisation and regression. Furthermore, many potential biomarkers of vascular disease have generated interest in terms of monitoring disease activity and the effect of therapeutic agents. However, despite much scientific promise with in vitro cell and animal models, there has been much less success in modulation of these processes in clinical practice. This review will highlight the local and systemic factors associated with disease progression and acute plaque destabilisation, the current role of therapeutic agents and the potential for targeted plaque modification.
A meta-analysis of antibiotic use for the secondary prevention of cardiovascular diseases
2008, Canadian Journal of Cardiology
A number of clinical trials have examined whether antibiotics decrease the incidence of adverse events in patients with cardiovascular diseases. However, results have occasionally been conflicting, and a meta-analysis may provide additional clarification.
To address whether antibiotic use can reduce the risk of future cardiac events among patients with established cardiovascular diseases.
PubMed and the Cochrane Central Register of Controlled Trials were searched using the key words “antibiotic” and “cardiovascular diseases”. Only randomized, placebo-controlled trials of patients with established cardiovascular disease and reporting cardiovascular outcomes were included. A random effects model was used and a fixed model was applied for sensitivity analysis.
A total of 393 papers published between January 1, 1994, and April 31, 2006, were initially identified. Thirteen trials (12,491 patients in the treatment group and 12,518 patients in the control group) were retained and included in the present meta-analysis. The pooled RR for the composite event end point, including death, myocardial infarction admission and unplanned revascularization procedures, was 0.96 (95% CI 0.90 to 1.04). No associations were seen for the individual outcomes of mortality (RR 1.07, 95% CI 0.96 to 1.19) or myocardial infarction/unstable angina (RR 0.96, 95% CI 0.85 to 1.07). Subgroup analyses based on patient populations (stable or unstable), type of antibiotics, or restricted to those with immunoglobulin G Chlamydia pneumoniae antibodies were also negative for a beneficial treatment effect. Similar results were found using a fixed effects model.
The meta-analysis did not provide evidence of an association between antibiotic use and the secondary prevention of cardiac events. Further research in this area does not appear to be promising.
Plusieurs essais cliniques ont analysé si les antibiotiques réduisent l’incidence d’effets indésirables chez les patients atteints d’une coronaropathie. Cependant, les résultats sont parfois contradictoires, et une méta-analyse pourrait clarifier la situation.
Vérifier si l’utilisation d’antibiotiques peut réduire le risque de futurs événements cardiaques chez les patients atteints d’une coronaropathie établie.
Les auteurs ont effectué des recherches dans PubMed et le Cochrane Central Register of Controlled Trials à l’aide des motsclés antibiotics et cardiovascular diseases. Les auteurs ont seulement inclus dans l’étude les essais aléatoires et contrôlés contre placebo des patients atteints d’une coronaropathie établie et dont l’issue cardiovasculaire était précisée. Ils ont utilisé un modèle d’effets aléatoires et ont appliqué un modèle fixe pour l’analyse de sensibilité.
Au total, les auteurs ont d’abord repéré 393 articles publiés entre le 1er janvier 1994 et le 31 avril 2006. Ils ont retenu et inclus 13 essais (12 491 patients dans le groupe traité et 12 518 dans le groupe témoin) dans la présente méta-analyse. Le RR groupé pour le point limite d’événement composite, y compris la mort, l’hospitalisation pour un infarctus du myocarde et des interventions de revascularisation non planifiées, s’élevait à 0,96 (95% IC 0,90 à 1,04). Les auteurs n’ont remarqué aucune association avec les issues personnelles de mortalité (RR 1,07, 95% IC 0,96 à 1,19) ou d’infarctus du myocarde ou d’angine instable (RR 0,96 95% IC 0,85 à 1,07). Les analyses de sous-groupes fondées sur la population de patients (stables ou instables), sur le type d’antibiotiques ou sur la restriction aux personnes possédant des anticorps aux Chlamydia pneumoniae de l’immunoglobuline G étaient également négatives à un effet bénéfique du traitement. Les auteurs ont obtenu des résultats similaires au moyen d’un modèle d’effets fixes.
La méta-analyse n’a pu démontrer une association entre l’utilisation d’antibiotiques et la prévention secondaire des événements cardiaques. Les recherches supplémentaires dans ce domaine ne semblent pas prometteuses.
Implications of antibodies to heat-shock proteins in ischemic heart disease
2008, International Journal of Cardiology
Experimental studies illustrate that priming with infectious agents, like Chlamydia pneumoniae, is involved in plaque formation and progression based on molecular mimicry with host heat-shock proteins (HSP). We have here evaluated the hypothesis that C. pneumoniae contributes to atherosclerotic disease progression via anti-HSP antibodies.
The blood circulation of 151 consecutive patients with ischemic heart disease was screened for antibodies against human and Chlamydia HSP60 and C. pneumoniae IgG. Antibody levels were associated with the angiographic extent of coronary atherosclerosis, with clinical symptoms of ischemic heart disease and with biochemical and functional endothelial dysfunction markers.
Positive serology to human (11%) or Chlamydia HSP60 (22%) was not associated with the presence and extent of atherosclerosis, neither was it related with endothelial dysfunction. Patients with acute myocardial infarction had significantly lower Chlamydia HSP60 antibody levels (median OD 0.12, range: 0.02–0.75) than patients with stable (median OD 0.22, range: 0.02–2.67) or unstable angina pectoris (median OD 0.24, range: 0–2.48) (p = 0.032). Subjects with positive C. pneumoniae IgG serology (if measured at a titre of 1:128) showed reduced flow-mediated vasodilation (p = 0.024), but vasodilation responses did not differ in single-, two- or three-vessel disease.
Overall, antibody responses to C. pneumoniae IgG, human or Chlamydia HSP60 are not associated with endothelial dysfunction and presence and severity of coronary artery disease, arguing against the suggestion that infection contributes to disease progression and supplying additional proof that C. pneumoniae is an unlikely major risk factor of coronary atherosclerosis.
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^f1: Corresponding author at present address: Suvi-Sirkku Kaukoranta-Tolvanen, Department of Bacteriology and Immunology, P.O. Box 21 (Haartmaninkatu 3), FIN-00014 University of Helsinki, Finland.

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Short communicationExpression of adhesion molecules on endothelial cells stimulated byChlamydia pneumoniae

Abstract

Short communication
Expression of adhesion molecules on endothelial cells stimulated byChlamydia pneumoniae