Chlamydia pneumoniae in atherosclerosis

Chlamydia pneumoniae is currently the infectious agent most often associated with the inflammation found in atherosclerosis. The seroepidemiological association and the actual presence of pathogen in lesions has been confirmed in numerous studies, in which technical difficulties seem to be the only limitation. Besides animal experiments and intervention trials, we need information of possible pathogenic mechanisms. Recently, several studies have suggested mechanisms by which C. pneumoniae infection could participate in the development of atherosclerosis.     

Inflammatory cells, apoptosis and Chlamydia pneumoniae infection in atherosclerosis

Chlamydia pneumoniae (CP), chromosomal alterations and apoptosis were suggested as contributing factors in the pathogenesis of atherosclerosis. Early (EP) and unstable plaques (UP) were studied in order to assess infiltrate composition, the apoptotic index, chromosome 7 stability and to investigate the concurrent presence of CP in EP and UP. Paraffin embedded sections of three iliac arteries and four aortas from young donors (EP), and four coronaries and nine carotid arteries (UP) were used. Aside from histological techniques, immunophenotypification for macrophages, T and B cells, smooth muscle and endothelial cells; FISH and DNA nick end labeling were performed. The amplifications with PCR for CP infection were negative in all specimens. In the EP, a focal myointimal thickening with foam cells and scarce smooth muscle cells was observed. Macrophages were most frequent in the intima (10.8%) while T and B cells were found in 2.3 and 1.5%. In the UP a thin cap covering a lipid-rich core with widespread vascularization and with severe luminal obstruction was observed. Macrophages were increased (21%), and T (1.5%) and B cells (3.5%) in the caps and inner areas of the lipid cores. At these sites, the FISH showed trisomy and tetrasomy of chromosome 7 and apoptosis was very frequent (10-30%). Macrophages in intimal lesions is one of the most prominent, consistent and permanent features in EP, and an elevated apoptotic index and chromosome 7 instability might contribute to evolution from stable to complicated plaques, while CP seems to play no role. However, further studies are needed with more cases to confirm this last observation.     

Chlamydia pneumoniae and atherosclerosis

There is widespread consensus that atherosclerosis is an inflammatory disease. Between possible pathogenetic mechanisms, infective hypothesis has received increasing attention. Researches have recently focused their attention on the role of Chlamydia pneumoniae, a gram-negative intracellular organism, as infection by this bacterium has been demonstrated frequently associated with atherosclerosis. This review attempts to analyze and critically evaluate available data of the literature about the association between Chlamydia pneumoniae and atherosclerosis in order to provide updated elements of judgement concerning a possible future revolutionary scenario: the consideration of atherosclerosis as an infective disease, susceptible to prevention and treatment by means of antimicrobial therapy. More than twenty sero-epidemiological studies have found a two-fold or greater risk of cardiovascular events in subjects with serological evidence of Chlamydia pneumoniae infection. The organism has been identified in over 50% of atherosclerotic plaques examined by various histopathological techniques, while it has been only rarely found in normal artery tissues; moreover, viable Chlamydia pneumoniae has recently been isolated from coronary and carotid atherosclerotic plaques. Several experimental studies have shown that the biological properties of Chlamydia pneumoniae can explain its potential role in initiating and/or modulating plaque formation. The most relevant issue, i.e. the possibility of preventing or slowing progression of the disease with antimicrobial treatment, is still unsolved: only data from experimental studies on animals and four small intervention trials on humans are available, and their encouraging results require confirmation in larger prospective studies. In conclusion, while the association between Chlamydia pneumoniae and atherosclerosis seems to be established, it is still uncertain whether or not the organism plays a causal role in atherosclerosis and its complications. It is hoped that the results of wide scale clinical intervention trials with antibiotics for the secondary prevention of atherosclerotic diseases now in progress will clarify this problem.     

Chlamydia pneumoniae and atherosclerosis

Chlamydia pneumoniae is the third species of the genus Chlamydia and has been known to cause respiratory tract infections. Since the association between the seropositivity of C. pneumoniae and ischemic heart diseases was reported in 1988, the association between C. pneumoniae and atherosclerosis has been noteworthy. Positive findings of the association between C. pneumoniae and atherosclerosis have been reported as the result of seroepidemiological surveys, histological studies to detect C. pneumoniae in human atherosclerotic tissues, and animal infection models. These data supported that C. pneumoniae infection occurs in human vascular walls and may accelerate the foam cell formation of macrophage and smooth muscle cells, and may play a causative role in atherosclerosis. Several large-scale studies of the antimicrobial prevention of secondary cardiac events are in progress. The genome projects for C. pneumoniae have recently been reported. A number of issues remain unclear, however, and further intensive research is necessary.     

Chlamydia pneumoniae and atherosclerosis

OBJECTIVE: To review the literature for evidence that chronic infection with Chlamydia pneumoniae is associated with atherosclerosis and acute coronary syndromes. DATA SOURCES: MEDLINE and Institute of Science and Information bibliographic databases were searched at the end of September 1998. Indexing terms used were chlamydi*, heart, coronary, and atherosclerosis. Serological and pathological studies published as papers in any language since 1988 or abstracts since 1997 were selected. DATA EXTRACTION: It was assumed that chronic C pneumoniae infection is characterised by the presence of both specific IgG and IgA, and serological studies were examined for associations that fulfilled these criteria. Pathological studies were also reviewed for evidence that the presence of C pneumoniae in diseased vessels is associated with the severity and extent of atherosclerosis. DATA SYNTHESIS: The majority of serological studies have shown an association between C pneumoniae and atherosclerosis. However, the number of cases in studies that have reported a positive association when using strict criteria for chronic infection is similar to the number of cases in studies which found no association. Nevertheless, the organism is widely found in atherosclerotic vessels, although it may not be at all diseased sites and is not confined to the most severe lesions. Rabbit models and preliminary antibiotic trials suggest that the organism might exacerbate atherosclerosis. CONCLUSION: More evidence is required before C pneumoniae can be accepted as playing a role in atherosclerosis. Although use of antibiotics in routine practice is not justified, large scale trials in progress will help to elucidate the role of C pneumoniae.     

Chlamydia pneumoniae and atherosclerosis

Chlamydia pneumoniae is a human respiratory pathogen that causes acute respiratory disease. Multiple studies have associated C. pneumoniae with cardiovascular disease including seroepidemiologic studies, direct detection of the organism within the lesion, and isolation of the organism from atheromatous tissue. The most critical question to be answered by researchers in the field is whether C. pneumoniae plays a role in atherogenesis. This review summarizes in vitro studies, results in animal models of C. pneumoniae infection and atherogenesis, and human intervention studies that provide some support of a mechanistic role.     

Chlamydia pneumoniae and atherosclerosis

Chlamydia pneumoniae (C. pneumoniae) is a common respiratory pathogen. Many reports have documented the presence of C. pneumoniae in atheromatous coronary arteries, aorta, carotid arteries, and peripheral arteries using a variety of techniques. There is clear experimental evidence that C. pneumoniae can infect macrophages, endothelial cells, smooth muscle cells, and induce the formation of foam cells. Evidence from basic research and epidemiologic studies suggest that C. pneumoniae can induce macrophage foam cell formation by dysregulating native LDL uptake or metabolism (or both). Relatively small, secondary prevention studies, have suggested that antibiotic therapy might reduce monocyte activation and C. pneumoniae antibody titers, reduce inflammatory markers and possibly reduce adverse cardiovascular events. It is possible that C. pneumoniae enhances atherogenesis by causing inflammation and eliciting immune responses and may be one of the factors contributing to this multifactorial disease process.     

Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice.

Accumulating evidence supports an association between Chlamydia pneumoniae infection and atherosclerosis. To determine whether there is a causal relationship, the effects of chronic infection with C. pneumoniae on the development of atherosclerosis in apolipoprotein E (apoE)-deficient mice were evaluated. Eight-week-old male apoE-deficient mice were inoculated intranasally with C. pneumoniae three times, at 8, 9, and 10 weeks of age. The combined area of atherosclerotic lesions in the lesser curvature of the aortic arch was measured en face by computer-assisted morphometry. The lesion area was 2.4-fold greater (P=.05) at 16 weeks of age and 1.6-fold greater (P=.05) at 20 weeks of age in infected mice than in control mice. There were no differences in total plasma cholesterol levels between groups. This study demonstrates that C. pneumoniae infection accelerates the progression of atherosclerosis in the aortic arch of apoE-deficient mice.     

肺炎衣原体抗体IgA与动脉粥样硬化及再狭窄的相关性分析

目的 :探讨肺炎衣原体感染和炎症对冠状动脉 (冠脉 )粥样硬化和支架内再狭窄的影响。方法 :6 2 8例接受冠脉造影检查的患者根据造影结果分为冠脉粥样硬化组 (4 33例 )和非冠脉粥样硬化组 (195例 ) ,记录两组基线临床资料 ,检测血清肺炎衣原体抗体IgA及高敏的C反应蛋白 (CRP)。 2 6 1例冠脉内放置支架的患者分为感染组 (89例 )和非感染组 (172例 ) ,随访半年 ,再次冠脉造影检查 ,测量支架内管腔丢失率。结果 :冠脉粥样硬化组肺炎衣原体抗体IgA的阳性率及滴度均高于无冠脉粥样硬化组 (4 8.32 %∶2 6 .10 % ;1.31± 1.19∶0 .92± 1.12 ) ;血清CRP水平明显升高 [(34.6 7± 3.2 4 )mg/L∶(2 3.2 2± 3.2 7)mg/L],且随着病变程度加重而增加。肺炎衣原体感染组和非感染组再狭窄发生率分别为 2 7.0 %、2 1.3% ,差异无统计学意义。但有再狭窄者血清CRP水平明显高于无再狭窄者 [(36 .13± 4 .0 4 )mg/L∶(16 .5 1± 3.92 )mg/L]。 结论 :血清抗肺炎衣原体抗体IgA阳性与冠脉粥样硬化相关 ,但不能预示支架内再狭窄的发生 ;而CRP与冠脉粥样硬化和再狭窄的发生均相关 ,提示炎症反应不仅在动脉粥样硬化而且在支架内再狭窄的发生中均扮演重要角色。     

肺炎衣原体抗体IgA和CRP与冠状动脉粥样硬化及再狭窄的相关性研究

目的探讨肺炎衣原体感染和炎症对冠状动脉粥样硬化和支架内再狭窄的影响.方法628例接受冠状动脉造影检查的患者根据造影结果分为冠状动脉粥样硬化组(n=433)和非冠状动脉粥样硬化组(n=195),记录两组基线临床资料、检测血清肺炎衣原体抗体IgA及C-反应蛋白(CRP).92例放置冠状动脉内支架的患者分感染组(n=49)和非感染组(n=53),随访0.5年,再次冠状动脉造影检查,测量支架内管腔丢失率.结果冠状动脉粥样硬化组肺炎衣原体抗体IgA的阳性率及滴度均高于非动脉粥样硬化组(48.32%,26.1%,P=0.000;1.31±1.19,0.92±1.12,P=0.000);血清CRP水平明显升高(34.67±3.24,23.22±3.27,P=0.008),且随着病变程度加重而增加.肺炎衣原体感染组和非感染组内膜增厚发生率分别为(64.7%,63.3%,P=0.909),差别无显著性.但有内膜增厚者血清CRP水平明显高于无内膜增厚者(36.13±4.04,16.51±3.92,P=0.042).结论肺炎衣原体感染与冠状动脉粥样硬化相关,但不能预示支架内再狭窄的发生;而炎症标志物与冠状动脉粥样硬化和再狭窄的发生均相关,提示炎症反应不仅在动脉粥样硬化而且在支架内再狭窄的发生中扮演重要角色.     

The evolving relationship between Chlamydia pneumoniae and atherosclerosis

A body of evidence supports an association between Chlamydia pneumoniae and atherosclerosis. Recent prospective, seroepidemiologic studies have refined estimations of relative risk. Advances in diagnostic testing with the polymerase chain reaction have created a potential opportunity to screen for infected individuals. New insights into the pathogenesis of infection with C. pneumoniae have been reported, many of which are relevant to the development of atherosclerotic plaque. Clinical trials have now been initiated and should provide guidance as to the utility of antibiotics in the treatment or prevention of coronary artery disease.     

The development of asthma in wheezing infants with Chlamydia pneumoniae infection.

Chlamydia pneumoniae infection might play a role in the pathology of asthma, but its role in infantile asthma remains obscure. The presence of Chlamydia pneumoniae was serologically determined in wheezing infants who were then re-examined 1-year later to determine whether or not asthma is associated with this type of infection. Wheezing infants progressed to asthma more frequently after infection with Chlamydia pneumoniae than those who were not infected. These findings suggested that Chlamydia pneumoniae infection triggers asthma in wheezy infants.     

The relation between Chlamydia pneumoniae and atherosclerosis.

Dilatation of the brachial artery occurs after flow is increased, and an attenuation in this response is seen in subjects with cardiovascular risk factors, and in those with established coronary artery disease. The mechanisms linking ischaemia, flow changes, and brachial artery dilatation are unclear, and it is not known how these are affected by arterial disease. For the present it might be more appropriate to refer to flow associated rather than flow mediated dilatation, to describe the phenomenon in the brachial artery. Despite these caveats, the non-invasive measurement of brachial artery following ischaemic dilatation represents a significant advance, and its suitability as a surrogate marker for coronary artery dysfunction appears promising. The technique has potential as a tool for screening those at high risk of vascular disease, and as a surrogate endpoint in intervention studies. Further research should clarify the mechanisms involved, and lead to greater insights into the nature of endothelial dysfunction and cardiovascular disease.     

Chlamydia pneumoniae in otorhinolaryngological infection

I detail clinical observation, examination, and treatment of regional otorhinolaryngological infection 3-cases of acute sinusitis and 1 of acute pharyngitis-due to Chlamydia pneumoniae, occurring between January 2002 and December 2004. Special clinical features by infection with C. pneumoniae were not recognized in the 4 cases, while ordinary clinical features by conventional bacterial infection were recognized, such as pharyngalgia and pyrexia for acute pharyngitis and purulent discharge and headache for acute sinusitis. I diagnosed an infection for C. pneumoniae for 1 case with acute sinusitis by detecting a causative factor gene of C. pneumoniae by PCR. I diagnosed C. pneumoniae for the 2 other cases of acute sinusitis and the case of acute pharyngitis by confirming antibody titer of C. pneumoniae ascending by serological verification. The 1 adult acute sinusitis case and the acute pharyngitis case were treated using a new quinolone antimicrobial agent. I administered macrolides antimicrobial agent to the 2 acute pediatric sinusitis cases and attained good outcomes without recurrence. We wish to emphasize that C. pneumoniae infectionin in the otorhinolaryngological setting has not been adequately reported and has not received the attention it deserved. If a good outcome cannot be attained using the beta-lactam antimicrobial agent for otorhinolaryngological infection, it should be sought using a macrolides antimicrobial agent or the new quinolone antimicrobial agent for adults and with the macrolides antimicrobial agent for pediatric cases.