(Circulation. 1995;91:1320-1325.)
© 1995 American Heart Association, Inc.
Articles |
Late Lumen Loss After Coronary Angioplasty Is Associated With the Activation Status of Circulating Phagocytes Before Treatment
From the Department of Biochemistry (A.P., L.E.A.d.W., J.F.K., W.S.), the Catheterization Laboratory (M.K., P.W.S.), and the Department of Epidemiology and Biostatistics (T.S.), Erasmus University Rotterdam, The Netherlands.
Correspondence to Wim Sluiter, Department of Biochemistry, Cardiovascular Research Institute (COEUR), Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background The purpose of this pilot study was to identify biological risk factors for restenosis after percutaneous transluminal coronary angioplasty (PTCA) to predict the long-term outcome of PTCA before treatment.
Methods and Results To investigate whether blood granulocytes and
monocytes could determine luminal renarrowing after PTCA, several
characteristics of these phagocytes were assessed before angioplasty in
32 patients who underwent PTCA of one coronary artery and who had
repeat angiograms at 6-month follow-up. The plasma levels of
interleukin (IL)-1ß, tumor necrosis factor-
, IL-6, fibrinogen,
C-reactive protein, and lipoprotein(a) before angioplasty were assessed
as well. We found that the expression of the membrane antigens CD64,
CD66, and CD67 by granulocytes was inversely associated with the
luminal renarrowing normalized for vessel size (relative loss) at 6
months after PTCA, while the production of IL-1ß by stimulated
monocytes was positively associated with the relative loss. Next, these
univariate predictors were corrected for the established clinical risk
factors of dilation of the left anterior descending coronary artery and
current smoking, which were statistically significant classic
predictors in our patient group. Only the expression of CD67 did not
predict late lumen loss independent of these established clinical risk
factors. Multiple linear regression analysis showed that luminal
renarrowing could be predicted reliably (R2=.65;
P<.0001) in this patient group on the basis of the vessel
dilated and only two biological risk factors that reflect the
activation status of blood phagocytes, ie, the expression of CD66 by
granulocytes and the production of IL-1ß by stimulated monocytes.
Conclusions The results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote late lumen loss. To validate this new finding, further study in an independent patient group is required.
Key Words: angioplasty • leukocytes • prognosis • risk factors • stenosis
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Percutaneous transluminal coronary angioplasty (PTCA) is a nonsurgical treatment of obstructive coronary artery disease (CAD), which, despite its high initial success rate of 90%, is compromised by the occurrence of restenosis.1 To improve the long-term outcome of PTCA, the identification of risk factors for restenosis seems crucial.
The pathophysiology of restenosis has not yet been elucidated.2 It has been suggested that activated blood monocytes may contribute to this process by the production of cytokines and growth factors.1 3 4 The activation of granulocytes that occurs during PTCA, through the release of proteinases and oxygen-derived free radicals, may have a potential bearing on the development of restenosis as well.5
Circulating phagocytes are thought to reflect the in vivo state
of the immune defense.6 The different phagocyte functions
are mediated through specific membrane receptors. Members of the
integrin class of adhesion receptors (CD11/CD18) function in the
interaction of phagocytes with the endothelial lining,7
whereas receptors for the Fc moiety of IgG (CD16, CD32, and CD64) are
involved in the pinocytosis of immune complexes and the phagocytosis of
antibody-coated particles.6 The expression of these
membrane receptors can be stimulated by inflammatory mediators. For
example, interferon gamma induces de novo expression of the
high-affinity Fc receptor CD64 on granulocytes.8
N-Formylated peptides increase the expression of the
receptor for activated complement C3bi (CD11b/CD18) on both
granulocytes and monocytes.6 Activated granulocytes also
express increased levels of CD66 and CD67.9 In addition to
the stimulated expression of membrane receptors, inflammatory mediators
are capable of inducing a primed state in monocytes. In these primed
cells, the stimulated production of cytokines is
enhanced.10 Furthermore, stable, genetically determined
interindividual differences in the secretion of interleukin (IL)-1ß
and tumor necrosis factor (TNF)- by lipopolysaccharide
(LPS)-stimulated monocytes have been
demonstrated.11 12
To study whether circulating granulocytes and monocytes might contribute to the process of restenosis, we investigated whether luminal renarrowing after PTCA is associated with the activation status of circulating phagocytes.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Patient Group
Thirty-four patients gave informed consent for the study and were included according to the following criteria: (1) stable or unstable angina pectoris (not refractory to medical treatment); (2) one culprit lesion responsible for the complaints; and (3) successful PTCA according to angiographic and clinical parameters.13 The mean age of the patients (26 men and 8 women) was 54.2±8.3 years. The severity of the anginal complaints was classified according to the New York Heart Association: 8 patients were in class II, 17 were in class III, and 9 were in class IV. Nine patients had unstable angina (pain at rest and refractory to medical treatment). The target vessel was the left anterior descending coronary artery (LAD) in 17 patients, the left circumflex coronary artery (LCx) in 7 patients, and the right coronary artery (RCA) in 10 patients. Fifteen patients had suffered from myocardial infarction in the past, 6 patients had previously undergone PTCA, and in 2 patients coronary artery bypass graft surgery was performed before entrance into the study. The study population included 2 patients with diabetes mellitus, 22 patients with hypercholesterolemia (excluding 3 not known), and 21 patients with a family history of CAD. Sixteen patients were smokers; the 18 nonsmokers included patients who had stopped smoking at least 6 months before PTCA.
Protocol
Sheaths were inserted into the arterial and venous
femoral
vessels. To exclude any effect of day-to-day variation in the
biological risk factors under study, 30 mL of blood was collected from
the venous sheath immediately before treatment, anticoagulated with
0.2% EDTA, and kept at 4°C. Coronary angioplasty was performed with
a steerable, movable guide-wire system via the femoral route. Details
regarding the procedure used in our catheterization laboratory have
been reported.13 14 Angiograms were obtained before
and
directly after PTCA. Six months after the procedure, the patients were
scheduled for follow-up angiography. The angiograms before and after
PTCA and at 6-month follow-up were analyzed with the Coronary
Angiographic Analysis System as described
previously.13 14
When serious complaints of angina recurred before the 6-month
follow-up, intercurrent coronary angiography was performed. If
restenosis of the dilated segment was established, PTCA was repeated
and the angiogram at that time (n=6 patients) was considered to be the
end point for the study. Of the 34 patients who met the inclusion
criteria, 32 repeat angiograms were obtained; 2 patients refused
follow-up.
Luminal Loss
The continuous variable luminal loss is defined
as the change in
minimal lumen diameter (MLD) during follow-up normalized for vessel
size according to the following equation: relative loss (RLOSS) =
[(postintervention MLD-follow-up MLD)/vessel size] x
100%, and
reflects the degree of luminal renarrowing. The vessel size is the
value of the reference diameter function at the minimal position of the
obstruction as previously described.14
Reagents
The monoclonal antibodies (mAb) used in the flow
cytometric
analysis of membrane antigen expression were mAb B-B15 directed
against CD11a, mAb 44 against CD11b, mAb 3.9 against CD11c, mAb B-H8
against CD15, mAb YFC 120.5 against CD16, and mAb B-F1 against HLA-DR,
all obtained from Serotec. mAb IV.3 directed against CD32 and mAb 32.2
directed against CD64 were obtained from Medarex Inc. mAb CLB gran10
against CD66 and mAb B13.9 against CD67 were obtained from the Central
Laboratory for Blood Transfusion. mAb 5193, which recognizes
HLA-DR4, was from C-six Diagnostics Inc. The
fluorescein conjugate of the hexapeptide
N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys, which is recognized by the
receptor for N-formylated peptides on phagocytes, was
obtained from Molecular Probes.
Flow Cytometric Analysis of Membrane Antigens
The binding of
mAb to the cell surface was quantified by
fluorescence-activated cell sorting (FACStar, Becton Dickinson). A
buffy-coat fraction was obtained by centrifugation of the blood sample
at 850g for 10 minutes. Contaminating erythrocytes were
lysed in ammonium chloride solution consisting of 155 mmol/L
NH4Cl, 10 mmol/L NaHCO3, and 0.1 mmol/L
EDTA. Next, leukocytes were washed with PBS (pH 7.4) consisting of 140
mmol/L NaCl, 1.5 mmol/L KH2PO4, 8.1
mmol/L Na2HPO4·2H2O, and 2.7
mmol/L KCl, centrifuged at 400g for 10 minutes, and
resuspended in PBS with 2% fetal calf serum (FCS) and NaN3
(1 mg/mL). Leukocytes (4x105 cells) were incubated with
mAb for 30 minutes. Leukocytes were washed four times and then
incubated with fluorescein isothiocyanate (FITC)-conjugated anti-mouse
or anti-rat antibodies for 30 minutes, after which the cells were
washed four times and fixed with 1% paraformaldehyde in PBS with 2%
FCS for 24 hours at 4°C. Monocyte and granulocyte populations were
separated by gating on forward and perpendicular light scatter. Antigen
expression is presented as specific linear fluorescence intensity
(FI).
Cytokine Release
To assess the capacity of monocytes to
produce cytokines in
vitro, monocytes were isolated from the buffy-coat fraction, which was
reconstituted with PBS to 20 mL, layered on top of a Lymphoprep
gradient (Nycomed), and centrifuged at 800g for 10 minutes
at room temperature. The fraction containing the mononuclear leukocytes
was washed with PBS. Next, the erythrocytes were lysed in ammonium
chloride solution, and the remaining mononuclear leukocytes were washed
once with ammonium chloride solution and once with PBS and resuspended
in RPMI (Flow Laboratories) with 2% FCS. The percentage of monocytes
in this fraction was determined from cytospin preparations and in
general amounted to 25%. Cells (6.3x105) were transferred
into 96-well culture plates (Costar) and incubated at 37°C in a
humidified environment of 5% CO2/95% air in the
presence or absence of 5 ng/mL LPS according to the method described by
Endres et al.15 After 24 hours, supernatants were
collected and stored at -70°C until analysis of IL-1ß, IL-6,
and TNF- by an enzyme immunoassay (EIA, Medgenix). During this
incubation period, cell viability as determined by trypan blue dye
exclusion did not decrease significantly and was >95%. Cytokine
release was expressed in picograms per 104 monocytes.
Fibrinogen
High- and low-molecular-weight fibrinogen levels
were determined
with an EIA as previously described16 and expressed in
grams per liter.
C-Reactive Protein
C-Reactive protein (CRP) was measured with
an EIA (Dakopatts)
and expressed in milligrams per liter.
Lipoprotein(a)
The lipoprotein(a) [LP(a)]
concentration in plasma was
determined with a radioimmunoassay (Pharmacia) and expressed in
milligrams per liter.
Statistical Analysis
The variation in duplicate measurements
(intra-assay variation)
did not exceed 10%. The strength of the association of late lumen loss
with each of the potential biological risk factors described in the
previous sections was assessed by linear regression analysis. Each
new finding should be considered suggestive and needs validation in an
independent patient group. No attempt was made to correct for
multicomparisons, since it is not clear whether such a procedure is an
improvement here.17 18 Since the expression of
HLA-DR4 is a characteristic cells may or may not have, this
variable is treated as a categorical one (no expression=0,
expression=1). Each variable that proved to be statistically
significant (P<.05) in the univariate regression
analysis was assessed by multiple linear regression analysis to
establish whether it was a risk factor independent of established
clinical risk factors. The established risk factors included the vessel
dilated (P=.001; ß=.5495) (LAD=1,
other=0) and current
smoking (P=.024; ß=.3988) (yes=1,
no=0). Other risk
factors reported in the literature were not statistically significant
in the present study, ie, family history of CAD (P=.072;
ß=.3275), diabetes mellitus (P=.120;
ß=.2807),
hypercholesterolemia (P=.332; ß=.1867), unstable
angina
(P=.363; ß=.1665), hypertension
(P=.569;
ß=.1046), angina class (P=.674; ß=.0772)
(class I/II=0,
class III/IV=1), patient age (P=.826;
ß=.0405) (age <65
years=0; 
65 years=1), and sex (P=.882;
ß=.0274). The new
independent risk factors, together with the established clinical risk
factors, were used in a stepwise multiple linear regression
analysis with P values for inclusion and elimination set
at .05 and .10, respectively, to build a model that predicts the
luminal renarrowing.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Variables Predictive for Late Lumen Loss
To investigate whether circulating phagocytes could contribute to luminal renarrowing after PTCA, we determined the activation status of circulating phagocytes before treatment and assessed its association with the degree of luminal renarrowing (RLOSS) at 6 months after PTCA. We identified several new univariate predictors of late lumen loss, the expression of CD64, CD66, and CD67 by granulocytes, and the stimulated production of IL-1ß by monocytes (Table
; Figs
1 and 2). Next, the relative
importance of these new univariate predictors with respect to
established clinical risk factors was assessed. Multivariate regression
analysis showed that three of the new univariate predictors were
statistically significant independent predictors for luminal
renarrowing after PTCA (Table). CD66, an antigen expressed by
granulocytes only, showed an inverse association with the relative
luminal renarrowing at 6-month follow-up. This also was the case for
the expression of CD64, the high-affinity receptor for immunoglobulin G
(IgG). Furthermore, the RLOSS was positively associated with the amount
of IL-1ß produced by monocytes in response to LPS. No other variables
under study, including the plasma levels of LP(a), IL-1ß, TNF-,
and fibrinogen, showed a significant relation with late lumen loss
(Table).
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Multiple Regression Model to Predict Late Lumen Loss Before
PTCA
To obtain a model that predicts the RLOSS before treatment, the
relative contributions of the three new independent predictors of late
lumen loss and the two established risk factors were analyzed by
multiple regression using the stepwise procedure. This analysis
showed that the RLOSS can be predicted from the expression of the
activation marker CD66 (median, 7.8 FI; range, 0.0 to 22.4 FI) by
granulocytes, the production of IL-1ß (median, 119.4
pg/104 monocytes; range, 0.0 to 368.9 pg/104
monocytes) by stimulated monocytes, and the vessel dilated (LAD versus
RCA or LCx) according to the following equation:
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(R2=.65; P<.0001), with standard errors of 6.3, 0.5, 0.03, and 4.8 for the constant and the regression coefficients, respectively. The standardized regression coefficients (ß) of CD66, IL-1ß, and LAD amounted to -0.4671, 0.3055, and 0.4328, respectively.
Although it is fundamentally not
correct but merely an attempt to show
what could be expected of the model in an independent patient group, in
Fig 3 the relation between the predicted luminal
diameter loss, calculated on the basis of this equation, and the
observed relative loss is presented for each of our present
patients. It is clear, however, that definitive conclusions about the
predictive value of the model can be obtained only in an independent
patient group.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The major finding of the present study is that the activation status of phagocytes is associated with luminal renarrowing after PTCA. Predictors for the degree of late lumen loss include characteristics of monocytes (IL-1ß production) and granulocytes (expression of CD64 and CD66). These new predictors and two established clinical risk factors (vessel dilated and current smoking) were used to build a model by multiple linear regression analysis that predicts the RLOSS before treatment from (1) the production of IL-1ß by stimulated monocytes, (2) the expression of the activation marker CD66 by granulocytes, and (3) the vessel dilated (LAD versus LCx and RCA).
The amount of IL-1ß a monocyte can secrete upon stimulation is
genetically determined11 12 and depends on the primed
state of this type of phagocyte.10 19 It is assumed
that
IL-1 is an important determinant of intimal hyperplasia.20
In vitro studies have shown that IL-1 stimulates the thrombogenicity of
endothelial cells and elevates levels of platelet-derived growth factor
(PDGF)-A and PDGF-B chain transcripts in endothelial
cells.21 22 Since PDGF has been shown to stimulate
the
migration of smooth muscle cells into the intima,23 this
mechanism might be relevant. We found no relation between the degree of
luminal renarrowing after PTCA and the spontaneous release of IL-1ß
by blood monocytes in vitro or the IL-1ß level in the plasma before
treatment. However, the capacity of blood monocytes to synthesize
IL-1ß upon stimulation in vitro was associated with the late outcome
after PTCA. This led us to hypothesize that the patients' blood
monocytes, in a response to vascular injury, may infiltrate the lesion,
become stimulated, and depending on their capacity, secrete IL-1ß
that promotes intimal hyperplasia. Why only the stimulated production
of IL-1ß and not of IL-6 and of TNF- by monocytes is associated
with relative lumen loss is a matter of speculation. In the cascade
model for restenosis, Libby et al20 proposed that
macrophages, which are a major source of IL-1, by the early acute
cytokine generation evoke a secondary cytokine and growth factor
response from other types of cells in the lesion, including smooth
muscle cells and endothelial cells that might establish a positive,
self-stimulatory autocrine and paracrine feedback loop, amplifying and
sustaining the proliferative response.
We found an inverse association of relative luminal renarrowing with the expression of the high-affinity receptor for IgG (CD64) by granulocytes. Granulocytes express this antigen only after activation.8 However, CD64 did not significantly predict late lumen loss independent of the other multivariate predictors in our patient group. CD66, an antigen expressed exclusively by granulocytes, is considered to be an activation marker as well.9 Recent evidence suggests that the CD66 antigens function as presenter molecules of the sialylated Lewis(x) antigen that binds to endothelial leukocyte adhesion molecule-1 expressed by activated endothelial cells.24 The important finding of the present study was that the degree of late lumen loss was low if the expression of CD66 by granulocytes was high. This suggests that activated granulocytes in fact could serve a protective role in the process of luminal renarrowing after PTCA. In a way, this was an unexpected finding, since activated granulocytes are supposed to aggravate tissue damage by their potentially destructive armamentarium.5 However, the invasion of granulocytes at sites of injury is a normal response to injury that facilitates tissue repair. Could this be a likely initial response to PTCA as well? A number of independent findings indeed point in that direction. First, in the cuffed rabbit carotid artery model of restenosis, one of the earliest events is the infiltration of granulocytes into the lesion.25 The first 2 to 3 days of the inflammatory phase after PTCA may be crucial for the ultimate outcome.3 Second, granulocytes relax human (internal mammary) artery.26 And finally, some years ago it was found that granulocytes could have a significant biological role in preventing thrombosis, rather than augmenting thrombosis, by the generation of 6-keto-prostaglandin-E1 to inhibit platelet aggregation and by providing 13-hydroxy-octadecadienoic acid in the absence of endothelial cells to inhibit platelet adhesion.27 Since local thrombosis after PTCA might be a key event in the cascades of cytokine/growth factor production by macrophages and smooth muscle cells,20 a protective role of granulocytes could therefore be anticipated.
Recently it has been shown that granulocyte activation occurs directly after angioplasty.5 Our data indicate that the activation status of granulocytes before treatment may be crucial in limiting luminal renarrowing at 6 months after PTCA.
Taken together, we conclude that the degree of late lumen loss might be predicted before treatment from the amount of IL-1ß produced by stimulated monocytes, the expression of CD66 by granulocytes, and the vessel treated by PTCA. If our model reflects some major aspects of the process of lumen loss after PTCA, interventional therapy could be directed to the function of granulocytes and monocytes. The failure of a multicenter trial conducted to determine whether corticosteroids infused before PTCA could reduce the rate of restenosis28 indicates that broad-spectrum drugs are not a first choice and that timing to allow granulocytes to perform their beneficial role could be important. However, the model presented here first needs to be validated in an independent and larger patient group to establish its prognostic value.
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Acknowledgments |
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This study was supported by the Netherlands Heart Foundation grant 90.275. We thank Drs M. de Maat (Department of Internal Medicine II, Erasmus University Rotterdam) for the analysis of the plasma levels of fibrinogen and C-reactive protein, H. Jansen (Department of Biochemistry, Erasmus University Rotterdam) for the analysis of LP(a), and H. van Vliet (Department of Hematology, Erasmus University Rotterdam) for help with the flow cytometry.
Received November 10, 1994; revision received January 3, 1995; accepted January 10, 1995.
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 H. D. Danenberg, G. Golomb, A. Groothuis, J. Gao, H. Epstein, R. V. Swaminathan, P. Seifert, and E. R. Edelman Liposomal Alendronate Inhibits Systemic Innate Immunity and Reduces In-Stent Neointimal Hyperplasia in Rabbits Circulation, December 2, 2003; 108(22): 2798 - 2804. [Abstract] [Full Text] [PDF]
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F. Cipollone, C. Ferri, G. Desideri, L. Paloscia, G. Materazzo, M. Mascellanti, M. Fazia, A. Iezzi, C. Cuccurullo, B. Pini, et al. Preprocedural Level of Soluble CD40L Is Predictive of Enhanced Inflammatory Response and Restenosis After Coronary Angioplasty Circulation, December 2, 2003; 108(22): 2776 - 2782. [Abstract] [Full Text] [PDF]
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 J. Perree, T. G. van Leeuwen, R. Kerindongo, J. A. E. Spaan, and E. VanBavel Function and Structure of Pressurized and Perfused Porcine Carotid Arteries: Effects of in Vitro Balloon Angioplasty Am. J. Pathol., November 1, 2003; 163(5): 1743 - 1750. [Abstract] [Full Text] [PDF]
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H S Gurm, D L Bhatt, A M Lincoff, J E Tcheng, D J Kereiakes, N S Kleiman, G Jia, and E J Topol Impact of preprocedural white blood cell count on long term mortality after percutaneous coronary intervention: insights from the EPIC, EPILOG, and EPISTENT trials Heart, October 1, 2003; 89(10): 1200 - 1204. [Abstract] [Full Text] [PDF]
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F Cipollone, M Fazia, A Iezzi, B Pini, F Costantini, D De Cesare, L Paloscia, G Materazzo, E D'Annunzio, T Bucciarelli, et al. High preprocedural non-HDL cholesterol is associated with enhanced oxidative stress and monocyte activation after coronary angioplasty: possible implications in restenosis Heart, July 1, 2003; 89(7): 773 - 779. [Abstract] [Full Text] [PDF]
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 F. Versaci, A. Gaspardone, F. Tomai, F. Ribichini, P. Russo, I. Proietti, A. S. Ghini, V. Ferrero, L. Chiariello, P. Agostino Gioffre, et al. Immunosuppressive therapy for the prevention of restenosis after coronary artery stent implantation (IMPRESS study) J. Am. Coll. Cardiol., December 4, 2002; 40(11): 1935 - 1942. [Abstract] [Full Text] [PDF]
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 F. G.P. Welt and C. Rogers Inflammation and Restenosis in the Stent Era Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1769 - 1776. [Abstract] [Full Text] [PDF]
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 M. E. Korkmaz, E. Tayfun, H. Muderrisoglu, A. Yildirir, B. Ozin, M. Ulucam, and M. Turan Carbon Coating of Stents Has No Effect on Inflammatory Response to Primary Stent Deployment Angiology, September 1, 2002; 53(5): 563 - 568. [Abstract] [PDF]
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H. D. Danenberg, I. Fishbein, J. Gao, J. Monkkonen, R. Reich, I. Gati, E. Moerman, and G. Golomb Macrophage Depletion by Clodronate-Containing Liposomes Reduces Neointimal Formation After Balloon Injury in Rats and Rabbits Circulation, July 30, 2002; 106(5): 599 - 605. [Abstract] [Full Text] [PDF]
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H. D. Danenberg, F. G. P. Welt, M. Walker III, P. Seifert, G. S. Toegel, and E. R. Edelman Systemic Inflammation Induced by Lipopolysaccharide Increases Neointimal Formation After Balloon and Stent Injury in Rabbits Circulation, June 18, 2002; 105(24): 2917 - 2922. [Abstract] [Full Text] [PDF]
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 M. Cejna, J. M. Breuss, H. Bergmeister, R. de Martin, Z. Xu, M. Grgurin, U. Losert, H. Plenk Jr, B. R. Binder, and J. Lammer Inhibition of Neointimal Formation after Stent Placement with Adenovirus-mediated Gene Transfer of I{kappa}B{alpha} in the Hypercholesterolemic Rabbit Model: Initial Results Radiology, June 1, 2002; 223(3): 702 - 708. [Abstract] [Full Text] [PDF]
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 M. S Conte, G. A VanMeter, L. M Akst, T. Clemons, M. Kashgarian, and J. R Bender Endothelial cell seeding influences lesion development following arterial injury in the cholesterol-fed rabbit Cardiovasc Res, February 1, 2002; 53(2): 502 - 511. [Abstract] [Full Text] [PDF]
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D. H. Walter, S. Fichtlscherer, M. B. Britten, P. Rosin, W. Auch-Schwelk, V. Schachinger, and A. M. Zeiher Statin therapy, inflammation and recurrent coronary events in patients following coronary stent implantation J. Am. Coll. Cardiol., December 1, 2001; 38(7): 2006 - 2012. [Abstract] [Full Text] [PDF]
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S E Francis, N J Camp, A J Burton, R M Dewberry, J Gunn, A Stephens-Lloyd, D C Cumberland, A Gershlick, and D C Crossman Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary angioplasty Heart, September 1, 2001; 86(3): 336 - 340. [Abstract] [Full Text] [PDF]
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M.A Costa, L.E.A de Wit, V de Valk, P Serrano, A.J Wardeh, P.W Serruys, and W Sluiter Indirect evidence for a role of a subpopulation of activated neutrophils in the remodelling process after percutaneous coronary intervention Eur. Heart J., April 1, 2001; 22(7): 580 - 586. [Abstract] [PDF]
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D. H. Walter, S. Fichtlscherer, M. Sellwig, W. Auch-Schwelk, V. Schachinger, and A. M. Zeiher Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation J. Am. Coll. Cardiol., March 1, 2001; 37(3): 839 - 846. [Abstract] [Full Text] [PDF]
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F. Cipollone, M. Marini, M. Fazia, B. Pini, A. Iezzi, M. Reale, L. Paloscia, G. Materazzo, E. D'Annunzio, P. Conti, et al. Elevated Circulating Levels of Monocyte Chemoattractant Protein-1 in Patients With Restenosis After Coronary Angioplasty Arterioscler Thromb Vasc Biol, March 1, 2001; 21(3): 327 - 334. [Abstract] [Full Text] [PDF]
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A. Kastrati, W. Koch, P. B. Berger, J. Mehilli, K. Stephenson, F.-J. Neumann, N. von Beckerath, C. Bottiger, G. W. Duff, and A. Schomig Protective role against restenosis from an interleukin-1 receptor antagonist gene polymorphism in patients treated with coronary stenting J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2168 - 2173. [Abstract] [Full Text] [PDF]
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F. G. P. Welt, E. R. Edelman, D. I. Simon, and C. Rogers Neutrophil, Not Macrophage, Infiltration Precedes Neointimal Thickening in Balloon-Injured Arteries Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2553 - 2558. [Abstract] [Full Text] [PDF]
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M. Gottsauner-Wolf, G. Zasmeta, S. Hornykewycz, M. Nikfardjam, E. Stepan, P. Wexberg, G. Zorn, D. Glogar, P. Probst, G. Maurer, et al. Plasma levels of C-reactive protein after coronary stent implantation Eur. Heart J., July 2, 2000; 21(14): 1152 - 1158. [Abstract] [PDF]
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Y Hojo, U Ikeda, T Katsuki, O Mizuno, H Fukazawa, K Kurosaki, H Fujikawa, and K Shimada Interleukin 6 expression in coronary circulation after coronary angioplasty as a risk factor for restenosis Heart, July 1, 2000; 84(1): 83 - 87. [Abstract] [Full Text] [PDF]
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T. SUZUKI, S. ISHIWATA, K. HASEGAWA, K. YAMAMOTO, and T. YAMAZAKI Raised interleukin 6 concentrations as a predictor of postangioplasty restenosis Heart, May 1, 2000; 83(5): 578 - 578. [Full Text]
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T. Saitoh, H. Kishida, Y. Tsukada, Y. Fukuma, J. Sano, M. Yasutake, N. Fukuma, Y. Kusama, and H. Hayakawa Clinical significance of increased plasma concentration of macrophage colony-stimulating factor in patients with angina pectoris J. Am. Coll. Cardiol., March 1, 2000; 35(3): 655 - 665. [Abstract] [Full Text] [PDF]
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L. J. Feldman, L. Aguirre, M. Ziol, J.-P. Bridou, N. Nevo, J.-B. Michel, and P. G. Steg Interleukin-10 Inhibits Intimal Hyperplasia After Angioplasty or Stent Implantation in Hypercholesterolemic Rabbits Circulation, February 29, 2000; 101(8): 908 - 916. [Abstract] [Full Text] [PDF]
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A. Buffon, G. Liuzzo, L. M. Biasucci, P. Pasqualetti, V. Ramazzotti, A. G. Rebuzzi, F. Crea, and A. Maseri Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1512 - 1521. [Abstract] [Full Text] [PDF]
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K. Peter, M. Schwarz, C. Conradt, T. Nordt, M. Moser, W. Kubler, and C. Bode Heparin Inhibits Ligand Binding to the Leukocyte Integrin Mac-1 (CD11b/CD18) Circulation, October 5, 1999; 100(14): 1533 - 1539. [Abstract] [Full Text] [PDF]
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 Y. Furukawa, A. Matsumori, N. Ohashi, T. Shioi, K. Ono, A. Harada, K. Matsushima, and S. Sasayama Anti–Monocyte Chemoattractant Protein-1/Monocyte Chemotactic and Activating Factor Antibody Inhibits Neointimal Hyperplasia in Injured Rat Carotid Arteries Circ. Res., February 19, 1999; 84(3): 306 - 314. [Abstract] [Full Text] [PDF]
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J. K. Mickelson, M. N. Ali, N. S. Kleiman, N. M. Lakkis, T. W. Chow, B. J. Hughes, and C. W. Smith Chimeric 7e3 Fab (ReoPro) decreases detectable CD11b on neutrophils from patients undergoing coronary angioplasty J. Am. Coll. Cardiol., January 1, 1999; 33(1): 97 - 106. [Abstract] [Full Text] [PDF]
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 C. Rogers, E. R. Edelman, and D. I. Simon A mAb to the beta 2-leukocyte integrin Mac-1 (CD11b/CD18) reduces intimal thickening after angioplasty or stent implantation in rabbits PNAS, August 18, 1998; 95(17): 10134 - 10139. [Abstract] [Full Text] [PDF]
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D. J. M. Van Put, N. Van Osselaer, G. R. Y. De Meyer, L. J. Andries, M. M. Kockx, L. S. De Clerck, and H. Bult Role of Polymorphonuclear Leukocytes in Collar-Induced Intimal Thickening in the Rabbit Carotid Artery Arterioscler Thromb Vasc Biol, June 1, 1998; 18(6): 915 - 921. [Abstract] [Full Text] [PDF]
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D. I. Simon, H. Xu, S. Ortlepp, C. Rogers, and N. K. Rao 7E3 Monoclonal Antibody Directed Against the Platelet Glycoprotein IIb/IIIa Cross-reacts With the Leukocyte Integrin Mac-1 and Blocks Adhesion to Fibrinogen and ICAM-1 Arterioscler Thromb Vasc Biol, March 1, 1997; 17(3): 528 - 535. [Abstract] [Full Text]
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 E. Allaire and A. W. Clowes Endothelial Cell Injury in Cardiovascular Surgery: The Intimal Hyperplastic Response Ann. Thorac. Surg., February 1, 1997; 63(2): 582 - 591. [Abstract] [Full Text]
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P. R. Moreno, V. H. Bernardi, J. Lopez-Cuellar, J. B. Newell, C. McMellon, H. K. Gold, I. F. Palacios, V. Fuster, and J. T. Fallon Macrophage Infiltration Predicts Restenosis After Coronary Intervention in Patients With Unstable Angina Circulation, December 15, 1996; 94(12): 3098 - 3102. [Abstract] [Full Text]
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C. Rogers, F. G.P. Welt, M. J. Karnovsky, and E. R. Edelman Monocyte Recruitment and Neointimal Hyperplasia in Rabbits: Coupled Inhibitory Effects of Heparin Arterioscler Thromb Vasc Biol, October 1, 1996; 16(10): 1312 - 1318. [Abstract] [Full Text]
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