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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strong epidemiological and pathological evidence supports a role for Chlamydia pneumoniae infection in atherosclerosis and human coronary heart disease. Animal models have shown that C. pneumoniae disseminates hematogenously in infected monocytes and macrophages, while in vitro data suggest that infected macrophages can transmit C. pneumoniae infection directly to endothelial cells. Endothelial cells may be key in vivo targets for C. pneumoniae infection; given that these cells are important in regulating the dynamics of the vessel wall, we used cDNA microarrays to study the transcriptional response of endothelial cells to infection with C. pneumoniae. cDNA arrays were used to characterize the mRNA expression profiles for 268 human genes following infection with C. pneumoniae, which were compared to mRNA profiles of uninfected cells. Selected genes of interest were further investigated by reverse transcription-PCR throughout a 24-h period of infection. C. pneumoniae infection upregulated mRNA expression for approximately 20 (8%) of the genes studied. Genes coding for cytokines (interleukin-1), chemokines (monocyte chemotactic protein 1 and interleukin-8), and cellular growth factors (heparin-binding epidermal-like growth factor, basic fibroblast growth factor, and platelet-derived growth factor B chain) were the most prominently upregulated. In addition to these families of genes, increases in mRNA levels for intracellular kinases and cell surface receptors with signal transduction activities were observed. Time course experiments showed that mRNA levels were upregulated within 2 h following infection. These results expand our knowledge of the response of endothelial cells to C. pneumoniae by further defining the repertoire of C. pneumoniae-inducible genes and provide new insight into potential mechanisms of atherogenesis. In addition, the use of cDNA microarrays may prove useful for the study of host cell responses to C. pneumoniae infection during latent and replicative stages of infection and related pathology.
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PMID:cDNA array analysis of altered gene expression in human endothelial cells in response to Chlamydia pneumoniae infection. 1117 7

Among the models of dyslipidemia and atherosclerosis, a number of wild-type, naturally defective, and genetically modified animals (rabbits, mice, pigeons, dogs, pigs, and monkeys) have been characterized. In particular, their similarities to and differences from humans in respect to relevant biochemical, physiologic, and pathologic conditions have been evaluated. Features of atherosclerotic lesions and their specific relationship to plasma lipoprotein particles have been critically reviewed and summarized. All animal models studied have limitations: the most significant advantages and disadvantages of using a specific animal species are outlined here. New insights in lipid metabolism and genetic background with regard to variations in pathogenesis of dyslipidemia-associated atherogenesis have also been reviewed. Evidence suggests that among wild-type species, strains of White Carneau pigeons and Watanabe Heritable Hyperlipidemic and St. Thomas's Hospital rabbits are preferable to the cholesterol-fed wild-type animal species in dyslipidemia and atherosclerosis research. Evidence for the usefulness of both wild-type and transgenic animals in studying the involvement of inflammatory pathways and Chlamydia pneumoniae infection in pathogenesis of atherosclerosis has also been summarized. Transgenic mice and rabbits are excellent tools for studying specific gene-related disorders. However, despite these significant achievements in animal experimentation, there are no suitable animal models for several rare types of fatal dyslipidemia-associated disorders such as phytosterolemia and cerebrotendinous xanthomatosis. An excellent model of diabetic atherosclerosis is unavailable. The question of reversibility of atherosclerosis still remains unanswered. Further work is needed to overcome these deficiencies.
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PMID:Advances in experimental dyslipidemia and atherosclerosis. 1155 65

A casual association between Chlamydia pneumoniae infection and atherosclerosis remains unresolved but plausible. Evidence comes from sero-epidemiological data, pathological specimen examinations, animal models and in vitro experiments. A number of prospective antibiotic intervention trials targeted against C. pneumoniae infection in patients with coronary heart disease are now underway. We remain wary that C. pneumoniae infection can persist in cell lines (associated with atherosclerosis) despite antibiotic therapy and also that reactivation of infection can occur. Issues such as delineating the patient group that could be targeted for treatment, choice of optimal antibiotic regimens, duration of therapy and effective methods of monitoring treatment response remain controversial and, as yet, unresolved. The relevance of persistence of C. pneumoniae infection and potential antimicrobial resistance will require equal consideration.
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PMID:Antibiotic therapy in coronary heart disease--where do we currently stand? 1171 94

Chlamydia pneumoniae infection generally starts in the respiratory tract and probably disseminates systemically in the blood stream within alveolar macrophages. We investigated the prevalence of C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) in patients with acute ischaemic heart disease. Samples of blood were obtained from 93 consecutive patients with acute ischaemic heart disease and from 42 healthy subjects, for detection of C. pneumoniae DNA in PBMC by polymerase chain reaction (PCR) and for serology. C. pneumoniae DNA in PBMC was detected in 25.8% (24/93) of the patients with acute ischaemic heart disease and in 4.8% (2/42) of the healthy subjects (P=0.008). C. pneumoniae IgG was found in 76.3% of patients and in 45.2% of healthy subjects (P=0.0008) while C. pneumoniae IgA was found in 59.1% and in 33.3%, respectively (P=0.01). No correlation was found between anti-C. pneumoniae antibody titers and positive PCR results. The detection of C. pneumoniae DNA in PBMC may aid in selecting patients who may benefit from antibiotic treatment; however, to support this contention, longitudinal studies on patients treated with antibiotics would also be necessary.
Atherosclerosis 2001 Dec
PMID:Prevalence of Chlamydia pneumoniae in peripheral blood mononuclear cells in Italian patients with acute ischaemic heart disease. 1173 Aug 34

Clinical studies have suggested a causal or contributory role of Chlamydia pneumoniae infection in asthma and atherosclerosis. The activation of synthetic functions of smooth muscle cells (SMC) including the production of cytokines and growth factors plays a major role in the formation of fibrous atherosclerotic plaques as well as in structural remodelling of the airway wall in chronic asthma. In this study we demonstrated that C. pneumoniae induced the production of low levels of interferon (IFN)-beta in bronchial and vascular SMC when infected cells were treated with tumour necrosis factor-alpha (TNF-alpha). IFN-beta production was analysed by reverse transcription-PCR and enzyme-linked immunosorbent assay. The upregulation of IFN-beta was paralleled by an increase in mRNA levels of interferon regulatory factor-1 and interferon-stimulated gene factor 3gamma, two transcription factors activating the expression of the IFN-beta gene. In addition, C. pneumoniae infection enhanced the mRNA level of indoleamine 2,3-dioxygenase, an IFN-inducible factor mediating the restriction of intracellular chlamydial growth, in TNF-alpha-stimulated SMC. C. pneumoniae-induced IFN-beta production by SMC may modulate inflammation and tissue remodelling during respiratory and vascular infection.
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PMID:Interferon-beta induction by Chlamydia pneumoniae in human smooth muscle cells. 1175 Feb 16

Evidence linking Chlamydia pneumoniae infection to atherosclerosis and to atherothrombotic events has recently emerged. A primary candidate implicated in these pathogenetic events is the 60-kDa chlamydial heat shock protein (HSP60). Another putative candidate to activate a potential proinflammatory mechanism is the chlamydial outer membrane protein 2 (OMP2). We have generated both HSP60 and OMP2 recombinant antigens in a nondenatured form and shown that (i) the two antigens were highly immunogenic in mice and (ii) murine antisera thus generated recognized the native C. pneumoniae proteins. We measured by enzyme linked immunosorbent assay (ELISA) and immunoblot assay antibody titers to the recombinant antigens in samples from 219 patients with coronary heart disease (CHD), 179 patients with unstable angina (UA), 40 patients with acute myocardial infarction (AMI), and 100 age-, sex-, and risk factor-matched healthy controls. We also examined whether anti-HSP60 and/or anti-OMP2 antibodies correlated with anti-C. pneumoniae antibodies assessed by a commercial microimmunofluorescence (MIF) assay. Immunoglobulin G (IgG), but neither IgA nor IgM, antibodies against the two recombinant proteins were detected by ELISA. In particular, anti-HSP60 antibodies were detected in >99% of CHD patients versus 0% of the controls, whereas the proportions of anti-OMP2 positive subjects were >70 and 27%, respectively. Nonetheless, among CHD patients, similar frequencies of positive subjects and titers of anti-HSP60 or anti-OMP2 antibodies were present in UA and AMI subjects. The anti-OMP2, but not the anti-HSP60, antibodies showed high specificity. Consistently, high serological correlation was observed between IgG MIF titers and IgG ELISA reactivity to OMP2 but not to HSP60. Overall, the results of this study demonstrate a strong correlation between CHD and anti-HSP60 IgG levels, as measured by our in-house ELISA. They also suggest that recombinant OMP2 ELISA, because of its high specificity and strong correlation with MIF assay, could be a candidate diagnostic marker for C. pneumoniae infection, which would be of potential usefulness for its specificity and nonsubjective nature.
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PMID:Antibodies to 60-kilodalton heat shock protein and outer membrane protein 2 of Chlamydia pneumoniae in patients with coronary heart disease. 1177 31

Chlamydia pneumoniae infection has long been suspected as a possible cause of atherosclerosis and has been frequently detected in atheromatous plaques of the coronary arteries. Nevertheless, its distribution is not correlated to the severity or extent of the disease, but it would support the hypothesis that the organism may be an active factor in the pathogenesis of atherosclerosis. A group of patients with stable angina were examined as to whether or not the positivity of antibodies against Chlamydia pneumoniae modified cellular populations as mechanisms responsible for the alterations of inflammatory response. We concluded that the presence of IgG anti-C. pneumoniae antibodies do not participate in the activation of inflammatory mechanisms that may intervene in the genesis of atherosclerosis in patients with stable angina.
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PMID:Antibodies against Chlamydia pneumoniae and their relation to lymphocyte population levels. 1191 18

In the study presented here, peripheral blood specimens obtained from patients with atherosclerosis were examined for the presence of Chlamydia pneumoniae to determine whether these specimens can be used for routine testing. Chlamydia pneumoniae DNA was detected in 7 of 56 patients with carotid stenosis and in three of four patients with other atherosclerotic diseases, but it was not detected in any of 50 healthy controls or in any of 59 age- and gender-matched patients suffering from other nonatherosclerotic diseases. IgG antibodies indicative of an active Chlamydia pneumoniae infection were detected by microimmunofluorescence in two of nine PCR-positive patients but in none of 41 PCR-negative patients. Four of nine serum samples obtained from PCR-positive patients contained IgA antibodies compared to 5 of 41 samples obtained from PCR-negative patients.
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PMID:Chlamydia pneumoniae DNA in peripheral venous blood samples from patients with carotid artery stenosis. 1191 5

Recent studies suggest an association between Chlamydia pneumoniae infection with atherosclerosis, including cerebrovascular disease. We investigated the prevalence of Chlamydial seropositivity in patients with acute ischaemic stroke syndrome compared with age- and sex-matched control subjects. Specific antibodies (IgA) to C. pneumoniae were measured by microimmunofluorescence in both the clinical group (n=91) and the control group (n=112). Forty patients (43.9%) and 34 controls (30.3%) had positive IgA titres (P < 0.05). The pooled data from this and previous series yielded 45% of seropositivity in cerebrovascular patients vs. 19% in control subjects (P < 0.001). In conclusion, we suggest an association between chronic infection by C. pneumoniae and acute ischaemic stroke.
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PMID:Association between seropositivity to Chlamydia pneumoniae and acute ischaemic stroke. 1198 40

Recent studies have suggested the existence of a close relationship between Chlamydia pneumoniae infection and atherosclerosis. However, it has been speculated that C. pneumoniae infection is not associated with early atherosclerosis but with advanced atherosclerosis. In the present study, we test this hypothesis. In 524 consecutive patients who underwent cerebral angiography were recruited for the study. From the films obtained during angiography, percent stenosis of neck internal carotid artery was calculated according to the method of the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Serum C. pneumoniae IgG and IgA antibodies were measured by a commercial ELISA enzyme immunoassay kit. Cerebrovascular risk factors such as age, gender, hypertension, diabetes mellitus, hyperlipidemis and smoking were assessed by interview. Old age above 60 years and diabetes mellitus were found to be independent risk factors for carotid artery stenosis in this study after adjustment for cerebrovascular risk factors. When we defined carotid artery stenosis as the presence of greater than 30% stenosis of one artery, there was no association after adjustment for other risk factors between C. pneumoniae IgG and IgA seropositivity and the presence of carotid artery stenosis for any cut-off value of seropositivity. When we defined carotid artery stenosis as the presence of greater than 70%, there was also no association between C. pneumoniae IgG and IgA seropositivity and the presence of carotid artery stenosis for any cut-off value of seropositivity. These results suggest that C. pneumoniae infection is not associated with carotid artery atherosclerosis.
Atherosclerosis 2002 Jul
PMID:Chlamydia pneumoniae infection is not involved in carotid artery stenosis. 1204 35


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