From the Department of Medicine, Unit of Rheumatology, Karolinska
Hospital and Center of Molecular Medicine (J.F., R.W.); the Department of
Thoracic and Cardiovascular Surgery, Karolinska Hospital (C.G.-H.); the
Department of Medicine, Unit of Cardiovascular Medicine, Karolinska Hospital
(C.L., U.d.F.); and the Department of Epidemiology, Institute of Environmental
Medicine (U.d.F.); Karolinska Institutet, Stockholm, Sweden.
Correspondence to Johan Frostegård, Department of Medicine, Karolinska Hospital, 17176 Stockholm, Sweden.
Methods and Results—Seventy-three men with borderline
hypertension (BHT) and 73 age-matched normotensive (NT) men
(diastolic blood pressure, 85 to 94 and <80 mm Hg,
respectively) were recruited from a population screening program.
Antibody levels were determined by ELISA. Presence of carotid
atherosclerosis was determined by B-mode
ultrasonography, and 29 individuals had atherosclerotic plaques. BHT
men had significantly higher aEC and aß2GP1 levels of IgG class than
NT control subjects (P=0.029 and
P=0.0001, respectively). aEC levels of IgM class were
higher in BHT (P=0.012), but not aß2GP1 levels. There
was no correlation between aCL levels and BHT. Individuals with
atherosclerotic plaques had significantly higher aEC levels of both IgG
(P=0.042) and IgM subclasses (P=0.018)
than those without plaques, but no difference was found in aCL and
aß2GP1 levels. Endothelin and aECs of IgM class were significantly
associated.
Conclusions—We demonstrate the first evidence of a significant
elevation of aEC and aß2GP1 levels in borderline hypertension. These
findings provide a new link between hypertension and
atherosclerosis and indicate that humoral immune
reactions to the endothelium may play an important role
in both conditions.
These 81 individuals with BHT were invited to participate in the
present investigation, together with 80 age-matched male control
subjects from the original population who had a DBP
The study was approved by the local ethics committee of Karolinska
Hospital and was conducted in accordance with the Helsinki Declaration.
All subjects gave informed consent before entering the program of which
this study was a part. Of the 81 men with BHT and the 80 NT control
subjects who agreed to participate in the program, 73 in the BHT and 73
in the NT group completed all procedures of the present study. None
of the subjects had any other illnesses or were regularly using any
drugs known to influence blood pressure, metabolic
variables, or inflammatory variables.
Study Program
Analysis of Total Serum Immunoglobulin Levels
Cell Culture
Detection of Antibody Levels
IgG and IgM antibodies to cardiolipin (CL) were determined by ELISA
essentially as described.24 25
Antibody reactivity to ß2GP1 was detected by coating irradiated
Titertek 96-well polyvinylchloride microplates (Flow Laboratories) with
50 µL/well of 30 µg/mL ß2GP1 (Calbiochem B 18287) dissolved in
10 mmol/L HEPES, 150 mmol/L NaCl, pH 7.4 (HEPES buffer), at
4°C overnight. The plates were blocked with 0.3% gelatin for 1 hour.
After washing, the wells were incubated with 50 µL of
50-times-diluted samples for 1 hour at room temperature (2 mmol/L
of EDTA was included in buffer). Control assays were performed in the
absence of ß2GP1.
After 3 washings with PBS, the plates were incubated with 50
µL/mL of alkaline phosphatase–conjugated goat anti-human IgG
(Sigma A-3150) diluted 1:9000 or IgM (Sigma A-3275) diluted 1:7000 with
PBS at 37°C for 2 hours. After 3 washings, 100 µL of substrate
(phosphatase substrate tablets, Sigma 104; 5 mg in 5 mL diethanolamine
buffer, pH 9.8) was added. The plates were incubated at room
temperature for 30 minutes and read in an ELISA Multiskan Plus
spectrophotometer at 405 nm. Each determination was done in triplicate.
The coefficient of variation between triplicate tests was <5%.
Investigators were blinded, and patient and control samples were
mixed.
Cross-Reactivity Between Antibodies
Analysis of Plasma Lipoprotein, Insulin, IGFbp-1, and
Endothelin-1 Levels
Blood Pressure Measurements
Twenty-four-hour ambulatory blood pressure (24-ABP) was measured with
the auscultatory Del Mar Avionics P-IV (P-IV, model 1990, Del Mar
Avionics) every 15 minutes for the complete 24-hour period. Patients
completed a diary during the period, noting body posture, going to bed,
waking up, and so forth. Data were transferred to a computer unit at
the end of the period. Artifacts were defined as any of the following:
SBP<50 mm Hg, SBP>250 mm Hg, DBP>SBP, DBP<30
mm Hg, and DBP>150 mm Hg. No other editing was
performed.31
Carotid Ultrasound
Body mass index (BMI) was calculated as weight in kilograms/(height in
meters)2 as
described.33
Statistical Methods
The BHT men had significantly altered metabolic profiles,
with fasting hyperinsulinemia and
dyslipoproteinemia, as previously presented (Table 1
Antibody Levels
If individuals with carotid atherosclerotic plaques were excluded, the
aEC levels of IgM were significantly higher in BHT men than in the NT
group (0.24 versus 0.20; P=0.01). Likewise, the aß2GP1s of
IgG classes were significantly higher in BHT men than in the NT group
(0.22 versus 0.18; P<0.0001). If individuals with BHT were
excluded, the aEC levels of IgM were nonsignificantly higher in
individuals with carotid atherosclerotic plaques than in those without
(0.24 versus 0.20; P=0.09), whereas the aEC or aß2GP1
levels of IgG type did not differ (data not shown).
Individuals with plaque (n=29) had higher aEC levels of both IgG and
IgM types compared with individuals without (n=117). However, the
aß2GP1 levels of both IgG and IgM types did not differ between
individuals with plaque and those without (Table 3
Antibody levels to CL did not differ between the BHT and NT groups or
between individuals with plaque and those without. There was no
difference in antibody levels to ECs, ß2GP1, or CL between smokers
and nonsmokers (data not shown).
To exclude the possibility that differences in antibody levels simply
reflected enhanced total antibody levels, IgA, IgG, and IgM were
determined. There was no difference between the BHT group and control
subjects (IgG, 9.71±1.86 versus 9.76±2.31 mg/mL and IgM, 2.25±0.81
versus 2.1±0.88 mg/mL, respectively).
Correlations Between Antibody Levels
Cross-Reactivity Between Antibodies
Correlations to Metabolic Variables
However, there were interesting correlations between aß2GP1 but not
aEC or aCL levels and other indicators of the metabolic
syndrome, as shown in Table 5
There was a significant association between 24-ABP determinations and
aEC levels of IgG class in the BHT group (P=0.037) and the 2
groups together (P=0.0042) but not in the NT group alone.
Smoking was not correlated to the antibodies tested (data not
shown).
Age was not associated with aß2GP1 or aCL levels; however, there was
a correlation with aECs of IgM type (P=0.039) but not IgG
type.
BHT is a condition with only relatively minor
cardiovascular alterations compared with normal
individuals. The enhanced aEC level is therefore likely to reflect a
humoral immune response associated with very early changes in the
endothelium. Endothelial dysfunction
has been described in hypertension, eg, as an impaired vasodilatation
due to defective NO production,2 3 and
changes in the endothelium including loss of heparan
sulfate and sialic acid have been reported.35 It
is thus possible that aECs react with neoepitopes formed or exposed on
the endothelium, thus being secondary to changes
induced by metabolic factors. aEC levels may therefore be a
marker for endothelial dysfunction in apparently
healthy individuals like those in the present study. These
antibodies may initiate atherosclerotic lesions and also aggravate
changes induced by metabolic factors, by activation of
complement, deposition of immune complexes, induction of adhesion
molecules, and attraction of phagocytic cells, which taken together may
lead to aggravation and/or induction of
atherosclerosis.
An intriguing finding was the strong association of aECs of IgM type
with endothelin, the most potent vasoconstrictor
described.36 This finding is in line with recent
reports indicating that aECs from patients with autoimmune disorders
are related to endothelin levels37 and that aECs
induce endothelin release in cultured human endothelial
cells.38 Furthermore, endothelin levels in the
BHT men studied here were also enhanced, as reported
earlier.30 However, endothelin in sera has been
suggested to be a marker of endothelial damage in
individuals with autoimmune disorders,37 and it
is possible that the statistical association noted here is also related
to endothelial damage. However, the observation that
aECs were highly related to endothelin levels in BHT clearly raises the
possibility that aECs may actually induce hypertension via enhanced
endothelin production. Whether or not aECs are a cause or
effect of endothelial dysfunction or, most likely, a
combination of both, these antibodies may activate and cause
damage to the endothelium.
Chronic infections have been implicated as contributing factors for
development of atherosclerosis.39
It is possible that aECs are formed during
infections40 and exert a pathogenic effect on the
endothelium, thus providing a link between infections
and atherosclerosis. However, little is known about the
role of chronic infections in hypertension. aECs, aß2GP1s, and aCLs
all were present in most individuals. The
physiological role of these antibodies is not well
characterized, and it is not known whether under certain circumstances
they also may protect the endothelium against noxious
compounds. aECs present in hypertension may thus predispose to
early atherosclerosis and also actively participate in
the pathogenesis of atherosclerosis.
aß2GP1 levels of IgG type were enhanced in BHT, in contrast to aCLs,
for which no significant differences were noted either for IgG or IgM
antibody type. aCLs predispose to cardiovascular
events, including both arterial and venous thrombosis in
autoimmune disorders like SLE and in the antiphospholipid
syndrome,41 and in young patients with myocardial
infarction, enhanced aCL levels were detected.20
ß2GP1 has been implicated as a cofactor in antibody binding to
CL,21 and recent data indicate that ß2GP1 is
bound to oxidized phospholipids, thereby creating an immunogenic
complex.42
In autoimmune diseases, ß2GP1 has been shown to be a cofactor also
for aECs,43 and we demonstrate here that in BHT
as well, ß2GP1 is involved in the antigenicity of ECs, because
ß2GP1 competed with antibody binding to ECs, in addition to which,
aß2GP1 and aEC levels correlated strongly.
In antiphospholipid syndrome and also in SLE, aß2GP1s are related to
vascular complications, which may be predicted even better than by
aCLs.44 An exaggerated immune response to
ß2GP1, associated with endothelium, platelets,
lipoproteins, or other phospholipid-rich surfaces, may trigger local
reactions, including complement activation and immune complex
deposition, leading to increased risk of thrombosis.
aß2GP1s were correlated with plasma levels of insulin, IGFbp-1, and
calculated insulin resistance, suggesting an association with the
metabolic syndrome.28 29 30 31 32 33 34 This may
reflect changes in immune reactions secondary to metabolic
factors. aECs, on the other hand, were not significantly associated
with metabolic factors, indicating a difference from
aß2GP1s and possibly also that aECs do not only reflect
metabolic changes.
Hypertension and BHT have been shown to be associated with increased
carotid atherosclerosis.22
Several different mechanisms, including direct effects of the elevated
blood pressure levels on the arterial
wall,45 46 have been suggested. Conversely,
however, atherosclerosis may also be causally related
to hypertension47 by means of an impaired
endothelial function leading to a defective secretion
of nitric oxide.2 3 Clearly, the interaction
between atherosclerosis and hypertension is complex,
and the different possibilities are not mutually exclusive.
During recent years, the role of the immune system in
atherosclerosis has attracted increasing attention.
Activated T cells and monocytes are present in the lesions,
and oxLDL has been identified as a possible factor inducing the
inflammatory component of atherosclerosis, because
oxLDL activates lymphocytes and monocytes to antibody formation
and secretion of proinflammatory
cytokines.4 5 6 7 Furthermore, aß2GP1 has
been suggested to be involved in oxLDL-uptake by macrophages
antibodies48 and may therefore also play a role in early
atherosclerosis. Comparatively little is known about
the role of the immune system in
hypertension.10 11 One possibility is that
immunogenic HSPs are induced at lesion-prone sites by mechanical
stress, which may be enhanced in hypertension, and thus elicit an
immune response in the artery wall; this hypothesis may provide an
explanation of how mechanical stress, as in hypertension, may induce
atherosclerosis.12 An intriguing
finding was therefore the strong correlation between aEC and anti-HSP60
antibody levels, which suggest that HSP60 may be involved in the
antigenicity of ECs, and it is possible that increased stress to the
vascular wall, as may be present in BHT, enhances the HSP60
expression in the endothelium, which triggers an immune
reaction directed at HSP60 in endothelial cells.
Taken together, our results indicate that antibodies to
endothelial cells and to an associated plasma protein,
ß2GP1, may play an important role in the early stages of both
atherosclerosis and hypertension.
Received December 4, 1997;
revision received May 11, 1998;
accepted May 14, 1998.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Antibodies to Endothelial Cells in Borderline Hypertension
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—Antibodies to
endothelial cells (aECs) and to cardiolipin (aCLs) are
implicated in autoimmune diseases like systemic lupus erythematosus
vasculitis. ß2-Glycoprotein 1 (ß2GP1) is a
cofactor for aCLs. The present study investigated the possible role
of aECs, aCLs, and aß2GP1 in borderline hypertension.
Key Words: endothelium • antibodies • glycoproteins • atherosclerosis • hypertension
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
According to the
response-to-injury hypothesis, an initial event leading to
atherosclerosis is damage and/or activation of the
endothelium.1 The
endothelium has also been implicated in hypertension, a
leading risk factor for the development of
atherosclerosis, and several studies have demonstrated
signs of endothelial dysfunction in
hypertension.2 Furthermore, vascular tone is
regulated by the endothelium, as exemplified by nitric
oxide and endothelin-1, both secretory products of
endothelial cells (ECs).3
Atherosclerosis is a chronic inflammation in the
vascular wall, in which T cells and monocytes/macrophages,
possibly activated by oxidized LDL (oxLDL), play an important
role.4 5 6 7 The humoral immune system may also be
of great importance in atherosclerosis, and antibodies
to oxLDL have been demonstrated to be related to the degree of
atherosclerosis.8 9 In
hypertension, alterations of immune function, including decreased
T-cell responses and abnormalities in complement function, have been
reported, although available data are comparatively
scarce.10 11 We recently demonstrated that
antibody levels to immunogenic heat shock proteins (HSPs) are enhanced
in borderline hypertension (BHT), which may provide a link between
enhanced mechanical stress to the endothelium at
lesion-prone sites and
atherosclerosis.12 Enhanced
levels of antibodies to ECs (aECs) have been demonstrated in autoimmune
diseases, such as systemic lupus erythematosus
(SLE), rheumatoid arthritis with systemic manifestations, and
Wegener's granulomatosis, and also Crohn's disease and
vasculitis.13 14 15 16 17 A direct pathogenic role of the
antibodies has been suggested,18 but the
knowledge of the exact nature of antigens involved is
limited.19 Antibodies to cardiolipin (aCLs) have
been related to myocardial infarction,20 and
ß2-glycoprotein 1 (ß2GP1) is an
important cofactor for aCLs.21 To investigate the
role of aECs, antibodies to ß2GP1 (aß2GP1s), and aCLs in BHT and
early atherosclerosis, we studied a group of 146
middle-aged men in which BHT patients were compared with age-matched
control subjects. We report here that serum aEC and aß2GP1 levels are
enhanced in patients with BHT.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Study Groups
In 1985, a blood pressure screening program was started in
Åkersberga, a small community 35 km north of
Stockholm.22 All men 35 to 55 years old were
asked by mail to visit the primary health care center and have their
blood pressure measured. BHT was defined as diastolic blood
pressure (DBP) of 85 to 94 mm Hg, and by this criterion, 193
patients with BHT were identified. These individuals were followed up
with yearly visits for 3 years. At these follow-ups, 
20% of the
subjects became hypertensive and 20% normotensive (NT), with the major
change (13% to 15%) occurring already at the 1-year follow-up visit.
After 3 years, 81 men were still within the range for BHT on the basis
of repeated measurements over the entire time period. 
80 mm Hg at
the initial measurement. To obtain 80 age-matched control subjects, 105
NT men were asked to participate, of whom 23 declined to participate
and 2 had a DBP >80 mm Hg. The blood pressure of the control
subjects was measured on 2 occasions a few weeks apart. For the
subjects to participate in the study, their DBP had to be 80
mm Hg on both occasions. All blood pressure measurements during the
entire recruitment procedure and study period were performed by 1
person, a specially trained nurse.
All subjects were investigated according to the same schedule.
Men with BHT and their control subjects were investigated
simultaneously when possible and never more than 4 weeks
apart. Blood samples were taken between 8 and 9:30 AM,
after 8 to 12 hours of fasting. All samples were drawn after 15 minutes
of rest in the supine position.
Serum immunoglobulins, IgG, IgM, and IgA, were determined by
immunoturbidimetry. Specific anti-IgG, anti-IgM, and anti-IgA reagents
and calibrators were obtained from Dako. The turbidimetric reaction was
quantified in a Hitachi 911 analyzer by measurement of light
transmission at 340-nm wavelength.
ECs were isolated and cultured from 3- to 5-cm-long segments of
the saphenous vein derived from patients undergoing coronary
bypass surgery, as described in detail
previously.23 Briefly, the vein was rinsed and
then filled with a collagenase solution (0.1%,
Worthington). Harvested cells were routinely cultured in MEM (Gibco
BRL) with the addition of 40% pooled heat-inactivated
(56°C, 30 minutes) human serum, antibiotics, and cAMP-elevating
compounds. Two days before the experiments, the ECs were gently
detached with a 0.1% trypsin/0.02% EDTA (1:1) solution. The cells
were seeded on gelatin-coated plastic wells (24-well plates, Costar) at
a density corresponding to 100 000 cells/cm2 in
MEM containing only 30% human serum and antibiotics. The ECs were
characterized as endothelial by immunohistochemical
staining of von Willebrand factor–related antigen,
PGI2 production, and their typical
cobblestone appearance. In each experiment, cells from a single donor
from the fourth to seventh passages were used. The use of human great
saphenous veins was approved by the ethics committee at the Karolinska
Hospital.
Antibodies to ECs were detected essentially as described
earlier.13 The ECs were suspended in the
RPMI 1640 medium containing 20% heat-inactivated FCS and
seeded on the 96-well flat-bottom tissue culture plates at a density of
1x104 cells/well. After the ECs were incubated
for 2 days, the plates were washed 3 times with PBS, pH 7.4. The ECs
were fixed for 15 minutes at room temperature with 0.2%
glutaraldehyde. The fixed cells were washed 4 times in
the washing buffer (PBS/0.2% BSA). The plates were blocked by 200 µL
of blocking buffer (PBS/1% BSA and 0.1 mol/L glycine) for 1 hour at
room temperature. The serum samples were diluted 1:50 in washing
buffer, and 100 µL of this dilution was added to each well and
incubated at 37°C for 2 hours.
To investigate whether there was an immunological
cross-reactivity between antibodies tested, competition assays were
performed. Sera at a dilution giving 50% of maximal binding to the
compound coated were preincubated with ECs as indicated. The sera were
incubated overnight with the different competitors at 4°C, and
inhibition of binding to ECs was tested. The percentage of inhibition
was calculated as follows: Percent inhibition=(OD control-OD with
competitorx100)/OD control, where OD is optical density.
VLDL, LDL, and HDL were determined as previously
described.26 The insulin resistance was
calculated by the formula IR=fasting insulin/22.5
e-ln(fasting glucose); References 27 and
2827 28 ). Insulin-like growth factor–binding protein-1 (IGFbp-1) was
analyzed by radioimmunoassay.29
Endothelin-1 in plasma was analyzed by a competitive
immunoassay as described in detail earlier.30
An identical procedure was followed at each occasion during the
entire recruitment period. All blood pressure measurements were
performed with a mercury sphygmomanometer. The cuff was adjusted
according to the circumference of the arm and placed at the level of
the heart. Blood pressure was recorded as the mean of 2
measurements taken after 5 minutes of rest in the supine position.
Systolic blood pressure (SBP) and DBP were defined according to
Korotkoff sounds I and V.
The right and left carotid arteries were examined with a duplex
scanner (Acuson 128XP/5) and a 7.0-MHz linear array transducer. The
subjects were investigated in the supine position with the head turned
slightly away from the sonographer, as described
earlier.22 Plaque was defined as a localized
intimal-medial thickening of >1 mm and a 100% increase in
thickness compared with normal, adjacent wall segments. Plaque
occurrence was scored as present or absent. The cutoff point of
1 mm was based on results of a pilot study in newly diagnosed,
untreated hypertensive men and control subjects without other
cardiovascular risk factors recruited from the same
population screening as in the present study. In the pilot study,
none of the participants had intimal-medial thicknesses >1
mm.32 Plaque was screened for in the common,
internal, and external carotid arteries on both sides.
Variables were tested for skewness. For skewed
variables, nonparametric tests were used for
comparisons between the groups (Mann-Whitney U test),
whereas Student's t test was used for normally distributed
variables. Categorical variables were compared by the
2 test. Spearman rank correlation coefficients
were calculated to estimate interrelations between aECs,
metabolic variables, and blood pressure levels. The
significance level was set at P<0.05. Values in the text
are given as mean±SD.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Characteristics of Case and Control Subjects
Basic characteristics of the 2 study groups are presented
in Table 1
. The mean blood pressure level
in the NT group was 125/75 (±11/±5) mm Hg compared with 141/89
(±10/±2) mm Hg in the BHT group, which indicates a significant
difference. The BHT group also had a significantly higher BMI and
waist-to-hip ratio. The 2 groups were well matched for age.
View this table:
[in a new window]
Table 1. Basic Characteristics of the Study Groups 
; Reference
3333 ). In the BHT group, 26% of the subjects had plaque on one or both
sides; the corresponding figure for the NT group was 14% (19 versus 10
subjects, P=NS). The basal level of endothelin-1 was
significantly increased in the BHT group.
In the population as a whole, the aEC levels of both IgM and IgG
types were significantly higher in the BHT group than in the NT group
(Table 2). The aß2GP1 levels of IgG
type were significantly higher in the BHT group than in the NT group
(P<0.0001), whereas there was no significant difference in
IgM antibody levels (Table 2).
View this table:
[in a new window]
Table 2. Antibody Levels to ECs, ß2GP1, and CL in BHT and
NT Groups ).
View this table:
[in a new window]
Table 3. Antibody Levels to ECs, ß2GP1, and CL in
Individuals With or Without Atherosclerotic Plaques
The correlation between aECs, aCLs, and aß2GP1s are shown in
Table 4. There were significant
correlations between aEC, aCL, and aß2GP1 levels against both the IgG
and IgM isotypes. Furthermore, antibodies to HSP65, which we recently
found to be elevated in BHT,12 correlated
significantly with antibodies to ECs (P=0.02) but not with
antibodies to ß2GP1 or CL.
View this table:
[in a new window]
Table 4. Correlations Between Antibody Levels in BHT and NT
Groups (All Individuals)
To study possible cross-reactivity between the antibodies, we
performed competition experiments, with CL, ß2GP1, and ECs and
as a control an unrelated antigen, PPD. The sera were tested at
a dilution that gave 50% of maximal binding to ECs. To test whether
antibodies to ECs could be outcompeted by ECs themselves, serum
was added to wells for 24 hours, and then the serum was moved to
another plate coated with ECs. When inhibition >25% was considered
positive, ß2GPI inhibited serum binding to ECs in 6 of 7 subjects
tested but CL in only 1 individual. ECs could outcompete binding to ECs
in all individuals tested. In the Figure, the
inhibitory capacity of ß2GP1 compared with an unrelated
antigen, PPD, was tested. ß2GP1 inhibited binding to ECs, but PPD had
no effect.
View larger version (37K):
[in a new window]
Figure 1. Effect of ß2GP1 and an unrelated antigen, PPD, on serum
binding to ECs. Sera were incubated with 100 µg/mL of antigens as
indicated at 4°C overnight. After this, binding to ELISA plates
coated with endothelial cells was investigated. Results
are presented as mean of duplicate determinations.
In the population as a whole and the 2 groups separately, there
were no significant correlations between aECs, aß2GP1s, or aCLs and
lipoproteins, BMI, waist-to-hip ratio, or intimal-medial thickness
(data not shown). . aß2GP1
levels of IgG type correlated with insulin, IGFbp1, and insulin
resistance, and aß2GP1 levels of IgM type correlated with IGFbp1. An
intriguing finding was the correlation between aECs of IgM type and
endothelin in the BHT group (R=0.25,
P=0.039).
View this table:
[in a new window]
Table 5. Association Between Antibody Levels to ß2GP1 and
Metabolic Factors
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
The main finding in this report is that BHT is significantly
associated with aEC antibody levels of both IgM and IgG types and with
aß2GP1 levels of IgG type. Total antibody concentrations showed no
difference between control subjects and BHT patients, indicating that
the results do not simply reflect total Ig levels. Individuals with the
presence of carotid atherosclerosis as determined by
carotid ultrasound had significantly enhanced aEC levels compared with
individuals without carotid atherosclerosis. This is in
line with recent findings indicating that aEC levels are enhanced in
individuals who had undergone surgery because of established
atherosclerotic vascular disease.34 aECs of IgM
but not IgG type were enhanced in BHT compared with NT individuals
without atherosclerosis. These findings indicate that
both BHT and atherosclerosis may be related to
endothelial changes leading to B-cell activation and
thus antibody formation, but the relative contribution of BHT and
atherosclerosis remains to be elucidated.
Acknowledgments
This work was supported by the Swedish Medical Research Council,
the Swedish Heart Lung Foundation, the Foundation for Old Servants, the
King Gustaf V 80th Birthday Fund, the Swedish Society of Medicine,
Ostermans Fund, the Swedish Rheumatism Association, the Wibergs Fund,
the Dahlens Fund, the Hedbergs Fund, and the Nanna Svartz Fund. We are
grateful to Ulla Hellmark Augustsson for her help with blood pressure
measurements over the years and for help with blood sampling, to Anders
Hamsten for help with lipoprotein fractionation, to Suad Efendic for
help with insulin analysis, to Kerstin Brismar (IGFbp-1), to
Thomas Lundeberg (endothelin-1), and to Birger Andersson, CALAB,
for help with analysis of total antibody levels and antibody
levels to HSP65.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
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A. G. Pockley, R. Wu, C. Lemne, R. Kiessling, Ulf de Faire, and J. Frostegard Circulating Heat Shock Protein 60 Is Associated With Early Cardiovascular Disease Hypertension, August 1, 2000; 36(2): 303 - 307. [Abstract] [Full Text] [PDF]
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R. Wu, U. de Faire, C. Lemne, J. L. Witztum, and J. Frostegard Autoantibodies to OxLDL Are Decreased in Individuals With Borderline Hypertension Hypertension, January 1, 1999; 33(1): 53 - 59. [Abstract] [Full Text] [PDF]
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