(Circulation. 2001;103:1613.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Distribution of Chlamydia pneumoniae in the Human Arterial System and Its Relation to the Local Amount of Atherosclerosis Within the Individual
From the Department of Cardiology, University Medical Center Utrecht (A.V., G.P., M.P., A.H.S., D.P.V. de K., C.B.), and Interuniversity Cardiology Institute of the Netherlands (A.V., G.P., M.P., A.H.S., D.P.V. de K.), Utrecht, and Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment (P.J.M.R.), Bilthoven, The Netherlands.
Correspondence to Gerard Pasterkamp, MD, PhD, University Medical Center Utrecht, Experimental Cardiology Laboratory, Room G02-523, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. E-mail g.pasterkamp{at}hli.azu.nl
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Abstract |
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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
(r2=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.
Key Words: atherosclerosis • Chlamydia pneumoniae • pathology
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that is a common cause of respiratory disease.1 Infection with C pneumoniae seems to be geographically widespread, and a high population prevalence of antibodies against the microorganism has been found, suggesting that most people are infected.2 3
Increasing evidence exists that C pneumoniae might play a role in atherosclerotic disease. An association between the microorganism and atherosclerosis was first demonstrated in seroepidemiological studies.4 5 In addition, C pneumoniae has been detected in human atherosclerotic lesions by various techniques like polymerase chain reaction, immunohistochemistry, electron microscopy, and culture.6 Thus far, the presence of the microorganism has been studied in only 1 or a small number of arterial locations within the same individual. In addition, negative control samples without atherosclerosis were obtained from different individuals who were mostly not age matched. Concern about these controls has been expressed by others.6 Within the individual, the distribution pattern of C pneumoniae has not been described.
Studying the localization of C pneumoniae within individuals is the most appropriate method to study the relation between local plaque formation and the presence of C pneumoniae, thereby excluding interindividual variability. In 24 individuals, we studied the presence of C pneumoniae at 33 different arterial locations with and without atherosclerotic disease. The aims of the present study were to determine the distribution pattern of C pneumoniae in the human arterial tree and to study whether within the individual this distribution pattern is associated with the distribution of atherosclerosis.
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Methods |
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Postmortem, 24 donated corpses (11 men and 13 women; age, 81.9±9.9 years; history of cardiovascular risk factors unknown) were pressure fixed with 4% formalin in situ (pressure, age+100 mm Hg). In each corpse, arterial segments were dissected at 33 different locations: left and right (L+R) anterior, medial, and posterior cerebral arteries; basilar artery; common and internal carotid arteries (L+R); brachial arteries (L+R); radial arteries (L+R); ascending and abdominal aorta; pulmonary arteries (L+R); left anterior descending coronary artery; left circumflex coronary artery; right coronary artery; superior mesenteric artery; renal arteries (L+R); common, internal, and external iliac arteries (L+R); and femoral arteries (L+R). For each artery type, the location was standardized.
Of each artery, 1 paraffin section was stained for
C pneumoniae–specific membrane
protein. Sections were deparaffinized, and endogenous peroxidase was
blocked with methanol containing 2%
H2O2. Next, sections were
pretreated with 0.5% blocking solution (Roche) and incubated with a
monoclonal antibody directed against C
pneumoniae–specific membrane
protein7 (clone RR-402;
Washington Research Foundation) in a concentration of 5 µg/mL.
Biotinylated horse anti-mouse polyclonal antibody (Vector) was used as
secondary antibody. For detection, sections were incubated with
streptavidin–horseradish peroxidase followed by treatment with
diaminobenzidine/nickel substrate. The sections were counterstained
with Nuclear Fast Red (Merck). Adjacent sections were incubated with an
irrelevant primary monoclonal antibody of the same isotype (mouse
IgG3
, clone G19-143; Pharmingen). HEp2 cells (CCL23; American Type
Culture Collection) infected with C
pneumoniae strain TW-183 were used as positive control.
Mock-infected HEp2 cells were used as negative control.
A cell was considered positive when cellular immunoreactivity was observed. Immunoreactivity in the intima/plaque and media was categorized according to the following 4 grades: 3+, immunoreactivity in >50 cells; 2+, immunoreactivity in 10 to 50 cells; 1+, immunoreactivity in 2 to 9 cells; and 0, no immunoreactivity.
To assess the local amount of atherosclerosis, adjacent
sections were stained with Elastin-van Gieson stain. Microscopic images
of the cross sections were recorded on VHS videotape with a 3CCD video
camera. In each cross section, the lumen area, the area encompassed by
the internal elastic lamina (IEL), and the circumference of the IEL
were measured. Plaque area was calculated by subtracting the lumen area
from the measured IEL area. To avoid any distortion of the IEL area by
cutting, the corrected IEL area was calculated as follows: IEL area
corrected=(circumference IEL)2/4
. Area
stenosis is a measure of the amount of plaque in a cross section
corrected for arterial size and was calculated as follows: (plaque
area/IEL area corrected)x100%.
Under physiological conditions, the pulmonary artery is exposed to a lower pressure than the other artery types. Therefore, it is unknown whether the mechanisms underlying the development of atherosclerosis are the same for the pulmonary artery and the other artery types. Consequently, the pulmonary artery was not included in the analysis in which cross sections of multiple locations were pooled.
Statistical Analysis
Student’s t
test was used to compare area stenosis of cross sections with and
without immunoreactivity. A paired
t test was used to compare area
stenosis of cross sections with and without immunoreactivity within
individuals. Linear regression analysis was used to correlate the
percentage of arteries with immunoreactivity with the average area
stenosis of the individual. Values are presented as mean±SD. A value
of P<0.05 was considered
statistically significant.
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Results |
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From 24 individuals, 766 arterial segments were harvested. Appropriate staining was available of 738 cross sections (30.8±1.7 per individual). The staining of 28 cross sections could not be interpreted because of background staining. In all 24 individuals, immunoreactivity to C pneumoniae–specific antigen was observed in
1 artery.
Immunoreactivity to C
pneumoniae–specific antigen
(Figure 1
) was observed in 111 of 738 arterial segments
(15%). In 64 of these 111 cross sections (58%), immunoreactivity was
observed in <10 cells (the
Table).
In 77 cross sections, immunoreactivity was found in the plaque only; in
9 cross sections, in the media only; and in 25 cross sections, in both
the plaque and media. Mock-infected HEp2 cells and sections incubated
with the isotype antibody consistently showed no staining.
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The
Table
shows the number of arteries with immunoreactivity to
C pneumoniae–specific antigen
per artery type. The highest prevalences of immunoreactivity were found
in the abdominal aorta, common and internal iliac arteries, and
coronary arteries. Immunoreactivity was not observed in the radial
artery and medial cerebral artery. Immunoreactivity was predominantly
observed in artery types with the highest area stenosis (the
Table).
Pooling all cross sections of all individuals showed that area stenosis
in cross sections with immunoreactivity was larger than in cross
sections without immunoreactivity
(Figure 2). Within the individual, area stenosis was larger
in cross sections in which immunoreactivity was observed compared with
cross sections without immunoreactivity
(Figure 3A). Within the same individual, moreover, area
stenosis was associated with the presence of immunoreactivity within
the same artery type, eg, the coronary arteries. In 15 individuals,
coronary immunoreactivity to C
pneumoniae was observed in 1 or 2 of the 3 coronary
arteries. In these individuals, area stenoses of
C pneumoniae–positive and
–negative coronary cross sections were compared. Comparison of the
coronary arteries of the same individual revealed that area stenosis of
cross sections with immunoreactivity was larger than that of
nonstaining cross sections
(Figure 3B).
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In the individual, immunoreactivity was observed in 15±10%
of the studied arteries (range, 3% to 45%).
Figure 4 shows a histogram of the percentage of arteries
with immunoreactivity per individual. The histogram indicates that
there is wide variation between different individuals in the number of
arteries in which C pneumoniae
was detected. A significant correlation between the average area
stenosis of all studied arteries of the individual and the percentage
of arteries with immunoreactivity in that individual is shown in
Figure 5 (r2=0.56,
P<0.001).
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Discussion |
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The respiratory pathogen C pneumoniae is assumed to disseminate from the lungs to vascular tissue.8 9 Evidence that the microorganism plays a role in atherosclerotic disease is growing.10 Thus far, all studies analyzing the presence of C pneumoniae in human atherosclerotic arteries focused on only 1 or a limited number of locations within a single individual. In most of these studies, negative controls without atherosclerotic disease were obtained from another group of individuals. As previously reported,6 most controls that were used were younger, raising the question of whether the difference in prevalence was due to the age of the subjects rather than the condition of the vessels. Also, other interindividual variables, like smoking status,11 12 merit careful consideration. In addition, only a selection of artery types, like the coronary arteries, aorta, and carotid artery, was studied in adequate numbers to obtain representative results for these artery types. This is the first study in which the presence of C pneumoniae was systematically studied throughout the arterial system and related to atherosclerotic disease within the same individual. Therefore, interindividual variation in factors that influence infection and dissemination of C pneumoniae is controlled for, because both atherosclerotic and nonatherosclerotic arteries are studied within the same individual.
Distribution in Arterial System
Our results indicate that within the individual
C pneumoniae is widely
disseminated in the arterial tree. To the best of our knowledge, this
study adds the renal, superior mesenteric, basilar, and anterior and
posterior cerebral arteries to the list of artery types in which the
microorganism has been reported. Although the microorganism was
widespread, it was not randomly distributed in the human arterial tree.
Artery types in which the microorganism was highly prevalent included
the abdominal aorta, coronary arteries, and common and internal iliac
arteries, which are all known for their relation to clinically relevant
atherosclerosis. Detection of C
pneumoniae in these artery types is in accordance with
previous
findings.13 14 15 16 17
C pneumoniae seemed to be
preferentially located in atherosclerotic arteries, because even within
the arterial system of one individual, area stenosis was found to be
associated with the presence of immunoreactivity to
C pneumoniae
(Figure 3). Moreover, within the same individual, area
stenosis in the 3 coronary arteries was found to be positively
associated with immunoreactivity for C
pneumoniae, indicating that the association between
atherosclerosis and the presence of the microorganism persists within
the same artery type. In previous studies,
C pneumoniae was preferentially
found in atherosclerotic arteries compared with arteries without
atherosclerotic disease obtained from different
individuals.13 14 16
The results of the present study demonstrate that within a single
individual, C pneumoniae was
preferentially located in atherosclerotic
arteries.
Variation Between Individuals
Little is known about interindividual differences in
distribution of C pneumoniae in
the arterial tree. Among individuals, a wide range (3% to 45%) in the
percentage of arteries with immunoreactivity to
C pneumoniae was observed.
Figure 4 suggests that dissemination of
C pneumoniae is not an "all
or nothing" phenomenon, because then all arteries would show
C pneumoniae immunoreactivity
in one individual, whereas in other individuals, immunoreactivity to
C pneumoniae would be absent.
Multiple factors could influence the distribution of the microorganism
in the arterial tree and explain the observed variation between
individuals. The "atherosclerotic status" of the individual seemed
to be associated with the number of arteries in which
C pneumoniae was observed,
because the percentage of arteries with the microorganism present in an
individual was found to be associated with the average area stenosis
throughout the arterial system of the individual. Thus, the more
atherosclerosis there was within the individual, the more arteries in
which C pneumoniae was
prevalent were seen.
Role in Atherosclerosis
Because of the cross-sectional design of this study, we
are unable to determine whether C
pneumoniae colonizes atherosclerotic plaque when it already
exists or plays a role in the initiation of the plaque. Thus, although
the present study adds further evidence on the tight junction between
C pneumoniae and
atherosclerosis, it does not answer the basic question of whether
C pneumoniae plays a causative
role in atherosclerosis. Within the coronary arteries of the same
individual, however, we found a correlation between the amount of
atherosclerotic disease and the presence of
C pneumoniae. This is
consistent with the results of a recent autopsy
study18 in which samples
were obtained from 60 individuals. C
pneumoniae immunoperoxidase staining was detected in 80% of
individuals with severe atherosclerosis and in 38% of individuals with
mild atherosclerosis. In another recent
study,19 no association was
found between the Stary grading of the atherosclerotic lesion and the
presence of C pneumoniae in the
vessel wall, which seems to contradict our results. A difference in the
techniques used to detect the microorganism might explain the different
results. We detected a membrane protein of
C pneumoniae by
immunohistochemistry, whereas in the above-mentioned study,
C pneumoniae DNA was detected
by polymerase chain reaction. If C
pneumoniae would only initiate atherosclerotic disease, an
equal prevalence could be expected in plaques of all sizes. It might be
possible that C pneumoniae also
has a role in the progression of the atherosclerotic process.
Progression of the atherosclerotic lesion by
C pneumoniae infection has been
shown in rabbit20 and
murine21
models.
Study Limitations
Only a 4-µm-thick slice of each artery was studied.
This single sample likely gives an underestimation of the presence of
the microorganism in the total artery. We used immunohistochemistry to
detect C pneumoniae in arterial
tissue. The monoclonal antibody used is directed against a membrane
protein of C pneumoniae.
Presence of the membrane protein does not necessarily reflect the
presence of viable C
pneumoniae. The postmortem material used was obtained from
elderly individuals. Therefore, any reference to onset of
atherosclerotic disease is unreliable. Because of this advanced age,
one may also doubt reference to progression of atherosclerotic disease.
However, a previous postmortem study revealed that plaques obtained
from elderly individuals (>80 years) showed a comparable staining for
inflammatory cells as plaques obtained from younger
individuals.22
Conclusions
C pneumoniae
was preferentially located in artery types that are associated with
clinically relevant atherosclerosis. Within a single individual, the
distribution of C pneumoniae
was associated with the distribution of atherosclerosis. Between
individuals, a wide variation in the presence of
C pneumoniae in the arterial
system was observed. However, it should be emphasized that although
these results add further evidence of the association between
C pneumoniae and
atherosclerosis, they do not prove a causative or pathogenic role for
the microorganism in
atherosclerosis.
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Acknowledgments |
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This study was supported by the Sorbo Foundation. Dr Pasterkamp is a fellow of the Catharijne Foundation, Utrecht. We gratefully thank W.J.A. van Wolveren and S. Plomp, Department of Functional Anatomy, University Medical Center Utrecht, for technical assistance.
Received October 11, 2000; revision received December 1, 2000; accepted December 9, 2000.
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References |
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1. Grayston JT, Campbell LA, Kuo CC, et al. A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR. J Infect Dis. 1990;161:618–625.[Medline] [Order article via Infotrieve]
2. Grayston JT. Infections caused by Chlamydia pneumoniae strain TWAR. J Infect Dis. 1992;15:757–763.
3. O’Neill C, Murray LJ, Ong GML, et al. Epidemiology of Chlamydia pneumoniae infection in a randomly selected population in a developed country. Epidemiol Infect. 1999;122:111–116.[Medline] [Order article via Infotrieve]
4. Saikku P, Leinonen M, Matilla K, et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet. 1988;2:983–986.[Medline] [Order article via Infotrieve]
5. Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link? Lancet. 1997;350:430–436.[Medline] [Order article via Infotrieve]
6. Taylor-Robinson D, Thomas BJ. Chlamydia pneumoniae in arteries: the facts, their interpretation, and future studies. J Clin Pathol. 1998;51:793–797.[Medline] [Order article via Infotrieve]
7. Puolakkainen M, Parker J, Kuo CC, et al. Further characterization of Chlamydia pneumoniae specific monoclonal antibodies. Microbiol Immunol. 1995;39:551–554.[Medline] [Order article via Infotrieve]
8. Yang ZP, Kuo CC, Grayston JT. Systemic dissemination of Chlamydia pneumoniae following intranasal inoculation in mice. J Infect Dis. 1995;171:736–738.[Medline] [Order article via Infotrieve]
9. Moazed TC, Kuo CC, Grayston JT, et al. Murine models of Chlamydia pneumoniae infection and atherosclerosis. J Infect Dis. 1997;175:883–890.[Medline] [Order article via Infotrieve]
10. Saikku P. Chlamydia pneumoniae in atherosclerosis. J Intern Med. 2000;247:391–396.[Medline] [Order article via Infotrieve]
11.
Hahn DL,
Golubjatnikov R. Smoking is a potential confounder of the
Chlamydia pneumoniae–coronary
artery disease association. Arterioscler
Thromb. 1992;12:945–947.
12. Leinonen M, Saikku P. Interaction of Chlamydia pneumoniae infection with other risk factors of atherosclerosis. Am Heart J. 1999;138:S504–S506.[Medline] [Order article via Infotrieve]
13.
Kuo CC, Gown AM,
Benditt EP, et al. Detection of Chlamydia
pneumoniae in aortic lesions of atherosclerosis by
immunocytochemical stain. Arterioscler
Thromb. 1993;13:1501–1504.
14. Shor A, Kuo CC, Patton DL. Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. S Afr Med J. 1992;82:158–61.[Medline] [Order article via Infotrieve]
15. Campbell LA, O’Brien ER, Cappuccio AL, et al. Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues. J Infect Dis. 1995;172:585–8.[Medline] [Order article via Infotrieve]
16.
Ramirez JA, for
the Chlamydia
pneumoniae/Atherosclerosis Study Group. Isolation of
Chlamydia pneumoniae from the
coronary artery of a patient with coronary atherosclerosis.
Ann Intern Med. 1996;125:979–982.
17.
Ong G, Thomas BJ,
Mansfield AO, et al. Detection and widespread distribution of
Chlamydia pneumoniae in the
vascular system and its possible implications.
J Clin Pathol. 1996;49:102–106.
18.
Ericson K,
Saldeen TGP, Lindquist O, et al. Relationship of
Chlamydia pneumoniae infection
to severity of human coronary atherosclerosis.
Circulation. 2000;101:2568–2571.
19.
Thomas M, Wong Y,
Thomas D, et al. Relation between direct detection of
Chlamydia pneumoniae DNA in
human coronary arteries at postmortem examination and histological
severity (Stary grading) of associated atherosclerotic plaque.
Circulation. 1999;99:2733–2736.
20.
Muhlestein JB,
Anderson JL, Hammond EH, et al. Infection with
Chlamydia pneumoniae
accelerates the development of atherosclerosis and treatment with
azithromycin prevents it in a rabbit model.
Circulation. 1998;97:633–636.
21. Moazed TC, Campbell LA, Rosenfeld ME, et al. Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. J Infect Dis. 1999;180:238–241.[Medline] [Order article via Infotrieve]
22.
Pasterkamp G,
Schoneveld AH, van der Wal AC, et al. Inflammation of the
atherosclerotic cap and shoulder of the plaque is common and locally
observed feature in unruptured plaques of femoral and coronary
arteries. Arterioscler Thromb Vasc
Biol. 1999;19:54–58.
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