(Circulation. 2000;102:1549.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Value of Serum-Soluble Intercellular Adhesion Molecule-1 for the Noninvasive Risk Assessment of Transplant Coronary Artery Disease, Posttransplant Ischemic Events, and Cardiac Graft Failure
From the Methodist Research Institute (C.A.L., S.J.M., J.M.N., J.A.C.) and Department of Transplantation (D.E.P., P.C.K., H.G.H.), Clarian Health Partners (Methodist, Indiana University, Riley Hospitals), Indianapolis, Ind, and Department of Biostatistics and Epidemiology (D.R.N.), Cleveland Clinic Foundation, Cleveland, Ohio.
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Abstract |
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Background—Adhesion molecules on arterial endothelium have been implicated in spontaneous atherosclerosis and transplant coronary artery disease (CAD). We studied whether elevated serum-soluble intercellular adhesion molecule-1 (sICAM-1) during the immediate posttransplant period was a risk factor for CAD, posttransplant ischemic events, or cardiac graft failure.
Methods and Results—We initially studied serum sICAM-1 in a subset of 16 cardiac allograft recipients (5.5±0.7 samples per patient) to determine a cutoff point that best correlated with presence of arterial and arteriolar endothelial ICAM-1 in matching endomyocardial biopsies. The cutoff value was 308 ng/mL. Subsequently, we prospectively evaluated serum sICAM-1 in serial samples (5.3±0.1 per patient) obtained during the first 3 months after transplantation in a validation subset of 130 recipients and correlated early sICAM-1 levels with long-term outcome. Serum sICAM-1 >308 ng/mL correlated significantly with ICAM-1 on arterial and arteriolar endothelium (P=0.02). Cardiac allograft recipients with serum sICAM-1 >308 ng/mL had 2.67 (95% CI, 1.28 to 5.59, P=0.009) times greater risk of CAD and 3.63 (95% CI, 1.05 to 12.5, P=0.04) times greater risk of graft failure. Recipients with sICAM-1 >308 ng/mL also developed more severe CAD (P=0.009) and more ischemic events (P=0.03) after transplantation.
Conclusions—Serum sICAM-1 levels can be used to noninvasively assess risk of transplant CAD, posttransplant ischemic events, and cardiac graft failure.
Key Words: cell adhesion molecules • coronary disease • heart failure • risk factors • transplantation
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Introduction |
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Transplant coronary artery disease (CAD) is a leading cause of allograft failure in cardiac transplant recipients after the first year after transplantation.1 Several risk factors have been implicated in the development of spontaneous disease, and some of the traditional risk factors have been associated with development of transplant CAD.1 2 3 Adhesion molecule expression on the endothelium may be a risk factor for developing both spontaneous and transplant CAD.4 5 6
Adhesion molecules are expressed on arterial endothelium from lesions of transplant CAD.5 7 8 The development of transplant CAD is preceded by expression of intercellular adhesion molecule-1 (ICAM-1) on arterial and arteriolar endothelium,5 and adhesion molecules on arterial endothelium have been directly implicated in neointimal formation.7 Soluble adhesion molecules seem to be relevant, because the extent of human atherosclerosis is correlated with circulating levels.7 Interestingly, plasma-soluble ICAM-1 (sICAM-1) is a risk factor for coronary occlusion and myocardial infarction, supporting the idea that endothelial activation occurs early in atherothrombosis.6 We evaluated whether increased serum sICAM-1 during the first 3 months after transplantation was a risk factor for subsequent transplant CAD, ischemic events, or graft failure.
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Methods |
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Patients
Initially, we studied serum samples and corresponding endomyocardial biopsies (5.5±0.7 per patient) from 16 consecutive adult cardiac allograft recipients who received transplants between January and October 1989 to determine a value of sICAM-1 that best correlated with immunohistochemical findings for ICAM-1 within the biopsies. We then prospectively studied an additional 130 consecutive patients who received transplants between October 1989 and July 1997 to evaluate the relationship between sICAM-1 during the first 3 months after transplantation and subsequent outcome. Patients were enrolled if they survived at least 6 months after transplantation, had pretransplantation and serial endomyocardial biopsy specimens taken during the first 3 months after transplantation for light microscopy and immunohistochemical studies, and had angiographic or histopathological evaluations of coronary arteries.5 9 10 Coronary angiography was performed yearly and averaged 3.6±0.2 angiograms per patient. This study was approved by the Methodist Research Institute’s Institutional Review Board, and all subjects signed a consent form.
Triple-drug immunosuppressive therapy consisted of prednisone, azathioprine or mycophenolate mofetil, and cyclosporine. Prednisone was administered at an initial dose of 1 mg · kg-1 · d-1, tapered to 0.5 mg · kg-1 · d-1 during the first month, 0.2 mg · kg-1 · d-1 during months 1 through 2, and 0.1 mg · kg-1 · d-1 during months 3 through 12 after transplantation. Patients were maintained on this dose unless they developed steroid complications. Azathioprine was administered at a dose of 1.5 to 2.0 mg · kg-1 · d-1 and mycophenolate mofetil at a dose of 1 g twice a day. Cyclosporine was administered at an initial dose of 7 to 10 mg · kg-1 · d-1, tapered to 3 to 5 mg · kg-1 · d-1 to maintain a blood level of 300 to 480 ng/mL during the first 3 months, 180 to 360 ng/mL during months 3 through 6, 90 to 180 ng/mL during months 6 through 12, and 75 to 120 ng/mL at >12 months after transplantation, depending on renal function. Grades 3 and 4 rejection episodes were treated with steroids and rabbit antithymocyte globulin or OKT3. Rejection with hemodynamic compromise was defined as a decreased ejection fraction and clinical signs of low cardiac output treated with methylprednisolone and/or inotropic agents. Higher-dose immunosuppressants, calcium channel blockers, or lipid-lowering agents (statins) were used at the physician’s discretion without knowledge of serum or immunohistochemical data for ICAM-1. Ejection fractions were measured by radionuclide ventriculography. Ischemic events were defined as either (1) presence of nontraumatic sudden cardiac death, (2) need of a revascularization procedure (eg, coronary artery bypass surgery, percutaneous transcoronary atherectomy, or stent), (3) presence of clinically evident ischemia (eg, clinical myocardial infarction, anginal symptoms, segmental wall motion abnormalities at cardiac catheterization supplied by a stenotic or occluded coronary artery, or ischemia by dobutamine stress test), or (4) any combination thereof. Graft failure was defined as death associated with unexplained cardiac allograft dysfunction or biopsy-proven cellular rejection or need for a second transplant.
A control biopsy from the right ventricle was obtained before transplantation from all donor hearts. Endomyocardial biopsies were obtained by right cardiac catheterization at 7 to 10 days, every 2 weeks during the first 2 months, and at 3 months after transplantation. Cellular infiltrates were graded according to the International Society for Heart Transplantation.5 9 10 Cytomegalovirus disease was defined as clinical disease with evidence of tissue invasion by cytopathological and/or tissue culture criteria. Cytomegalovirus prophylaxis with ganciclovir was used in seronegative recipients with seropositive donors.
Determinations of sICAM-1
Serial serum samples for each recipient were obtained at the
time endomyocardial biopsies were performed and
stored at -75°C. Samples were thawed and assayed in duplicate for
sICAM-1 with an ELISA (R&D Systems). The minimum detectable
concentration (sensitivity) of sICAM-1 was 0.35 ng/mL. Laboratory
personnel were unaware of immunohistochemical data from biopsies or
patient outcome.
Criteria for Diagnosis of CAD
CAD was diagnosed as any decrease in luminal diameter, whether
in the left main coronary artery or primary or branch vessels,
and was classified as mild, moderate, or severe on the basis of the
most severe CAD reported in each coronary
angiogram.11 Annual arteriograms were compared with
identical projections in serial studies and evaluated by
side-by-side comparisons. The presence and severity of disease were
determined by a consensus of 2 experienced angiographers blinded to the
results of the serological or immunohistochemical studies for ICAM-1.
Progression of disease was evaluated by comparing serial angiograms
side-by-side with the baseline angiogram obtained the first year after
transplantation. To reduce the possibility of donor-transmitted CAD,
recipients having a normal angiogram the first year after
transplantation were studied during subsequent follow-up, and the first
annual angiogram was considered baseline. Coronary arteries
were examined histopathologically in recipients who died before their
first annual angiogram. The degree of luminal narrowing was estimated
visually and classified as mild, moderate, or
severe.12
Antibodies and Control Experiments
Endomyocardial biopsies were studied
immunohistochemically for ICAM-1 with monoclonal antibody LB-2 (Becton
Dickinson). Arteries and arterioles were identified with monoclonal
antibody to smooth-muscle–specific 
-actin (1A4, Biomakor).
Secondary antibodies consisted of affinity-purified
fluorochrome-labeled F(ab')2 antibody fragments
to mouse immunoglobulins (Protos ImmunoResearch). Control experiments
were performed as described.5 9 10
Immunohistochemistry
Biopsies were embedded in OCT compound (Miles), snap-frozen in
liquid nitrogen, and stored at -20°C. Cryostat sections (4
µm) were air-dried overnight without chemical fixation. Antibody
experiments were performed with primary antibodies and
fluorochrome-labeled secondary antibodies. Immunohistochemical data
were evaluated by 2 investigators unaware of the clinical outcome. The
precise vascular localization of ICAM-1 was performed as
described.5 The proportion of biopsies with
arterial and arteriolar endothelial ICAM-1
during the first 3 months after transplantation was then
calculated.5
Statistical Methods
Receiver operating characteristic analysis determined a
cutoff point for sICAM-1 that corresponded to the immunohistochemical
detection of arterial and arteriolar
endothelial ICAM-1 in the matching biopsy among the
initial subset of 16 allograft recipients. Recipients in the validation
subset (n=130) with sICAM-1 at or under the cutoff point and those with
sICAM-1 over the cutoff point were compared for incidence and severity
of CAD and rates of graft failure. Wilcoxon rank-sum tests (for
continuous and ordered variables) and Fisher’s exact tests (for
discrete variables) were used to compare demographic and
clinical-laboratory characteristics of the 2 groups. Any significant
variable was included in subsequent Cox regression (for the
interval to CAD and graft failure) and logistic regression (for
severity of disease and ischemic events) to determine the
significance of sICAM-1. Kaplan-Meier curves illustrated the rates of
CAD and graft failure of the 2 groups over time. Values of
P<0.05 were considered statistically significant. Summary
statistics were reported as mean±SEM. Statistical analyses
were performed with SAS version 6.12.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Among the initial subset of 16 allograft recipients, a cutoff point for sICAM-1 was determined that best correlated with the presence of arterial and arteriolar endothelial ICAM-1 in the biopsies (5.5±0.7 per patient) because such reactivity was never found in donor hearts before transplantation. Sensitivity and specificity of this association were maximized when a cutoff of 308 ng/mL was used (Figure 1
). With this
cutoff point, serial determinations (5.3±0.1 per patient) of sICAM-1
and matching endomyocardial biopsies obtained
during the first 3 months after transplantation were prospectively
analyzed in the subsequent 130 recipients. Thirty-three
recipients had sICAM-1 remaining 
308 ng/mL (average sICAM-1,
185.2±10.5 ng/mL). However, 97 recipients had 
1 samples exceeding
the cutoff point (average sICAM-1, 355.1±13.7 ng/mL). Most samples
from these recipients (52.8%; 2.8±0.2 per patient) showed serum
sICAM-1 >308 ng/mL, and 61 of 97 (62.9%) already had sICAM-1 >308
ng/mL 7 to 10 days after transplantation. The average within-patient
standard deviation was 92.3±7.8 ng/mL, and no relationship between
time after transplantation and sICAM-1 was found during the first 3
months after transplantation (P=0.68). A significant
correlation (P=0.02) was found between increased sICAM-1 and
ICAM-1 on arterial and arteriolar
endothelium of matching serial
endomyocardial biopsies (Table 1). Recipients with sICAM-1 >308
ng/mL had a significantly higher percentage of
endomyocardial biopsies with arterial
and arteriolar endothelial ICAM-1 (Figure 2).
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Demographic and clinical-laboratory data of the studied population are
shown in Table 2. Significant differences
were found for sex of recipient, age of donor, HLA-DR mismatches, and
presence of cytomegalovirus disease.
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We studied the relationship between sICAM-1 determinations performed
during the first 3 months after transplantation and subsequent
development of transplant CAD in 130 recipients followed up for
44.9±2.5 months after transplantation (Table 3). Recipients with sICAM-1 >308 ng/mL
developed significantly more CAD (P=0.02), developed CAD
earlier (P=0.009), developed more severe disease
(P=0.009), and had more disease progression
(P=0.04) than recipients with sICAM-1 remaining at or under
the cutoff point.
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To reduce the possibility of donor-transmitted disease, we
evaluated allograft recipients who had a normal angiogram the first
year after transplantation (n=97) and followed up this subgroup of
patients over a period of 37.2±3.0 months after the first angiogram.
Recipients who initially had sICAM-1 >308 ng/mL (n=67) developed
significantly more CAD (P=0.004) and more severe disease
(P=0.002) than recipients with sICAM-1 levels 308 ng/mL
(n=30) (Figure 3).
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Kaplan-Meier estimates indicated that 1-year CAD rates in recipients
with sICAM-1 remaining 308 ng/mL were 3.3±3.3%, compared with
23.0±4.3% among recipients with sICAM-1 >308 ng/mL (Figure 4).
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The average sICAM-1 level during the first 3 months after transplantation for allografts that remained free of CAD was 274.5±7.8 ng/mL, and for allografts that developed angiographically detectable CAD, the average sICAM-1 level was 344.0±18.4 ng/mL (P<0.001). Interestingly, these values were, respectively, under and over the cutoff of 308 ng/mL calculated with an initial subset of 16 allograft recipients.
We subsequently analyzed the relationship between sICAM-1 and
development of ischemic events during follow-up. Recipients
with sICAM-1 >308 ng/mL during the first 3 months after
transplantation experienced significantly more events
(P=0.03) than recipients with sICAM-1 308 ng/mL (Table
3).
We then studied the relationship between sICAM-1 and subsequent
allograft failure (Table 3). Recipients with sICAM-1 >308 ng/mL
during the first 3 months after transplantation experienced more graft
failure (P=0.03) and their grafts failed earlier
(P=0.04) than recipients with sICAM-1 308 ng/mL.
Interestingly, 87.1% of grafts that failed developed CAD, detected
either angiographically or histopathologically.
Kaplan-Meier estimates indicated that graft survival at 5 years was
86.3±7.5% in recipients with sICAM-1 308 ng/mL and 69.8±5.5% in
recipients with sICAM-1 >308 ng/mL (Figure 5).
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Multivariate analysis indicated that sICAM-1
was a significant risk factor for CAD and graft failure after
adjustment for demographic and clinical parameters found to
be different between the 2 groups (Table 4); therefore, our results were unlikely
to be due to confounding effects. Recipients with sICAM-1 >308 ng/mL
during the first 3 months after transplantation were at significantly
greater risk of CAD (relative risk, 2.67; 95% CI, 1.28 to 5.59) and
graft failure (relative risk, 3.63; 95% CI, 1.05 to 12.5) than
recipients with sICAM-1 remaining 308 ng/mL.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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We found that elevated serum sICAM-1 levels (>308 ng/mL) during the first 3 months after transplantation were associated with ICAM-1 in graft arterial endothelium and with subsequent development of transplant CAD, posttransplant ischemic events, and allograft failure (primarily associated with development of CAD). Immunopathological studies show increased expression of adhesion molecules in atherosclerotic plaques,7 and adhesion molecules are implicated in transplant CAD.7 8 Prevention of disease with monoclonal antibodies to ICAM-18 and reduction in neointimal formation in a carotid artery injury model of P-selectin–deficient mice7 support the involvement of adhesion molecules in developing atherosclerosis-like lesions. The association between atherosclerosis and increased soluble adhesion molecules also suggests that they are involved in arterial disease.4 6 Recent studies demonstrated that ICAM-1 has significant prognostic value for patients at risk of developing transplant CAD,5 cardiac allograft failure,5 or myocardial infarction.6
Adhesion molecule–mediated leukocyte–endothelial cell interactions were implicated in the development of spontaneous or transplant CAD.5 Cytokines could further facilitate expression of endothelial adhesion molecules, because increased expression of cell adhesion molecules or increased concentrations of soluble adhesion molecules have been related to graft rejection.13 However, this relationship is controversial.14 Our findings suggest that upregulation of ICAM-1 in cardiac transplant recipients is not caused by cellular rejection, because recipients with increased sICAM-1 did not have more rejection episodes. Adhesion molecules could be upregulated by preformed anti-endothelial antibodies15 associated with development of transplant CAD.16
Increased sICAM-1 could be associated with a viral infection. Virus-infected endothelial cells enhance ICAM-1 expression,17 and cytomegalovirus disease is associated with development of transplant CAD.1 However, other investigators showed lack of association between cytomegalovirus disease and transplant CAD.18 Although our data showed a relationship between sICAM-1 and cytomegalovirus disease, multivariate analysis failed to show an association between cytomegalovirus disease and CAD or graft failure. sICAM-1 increases with age19 and decreases with the presence of estradiol.20 However, donor age and recipient sex are probably not major factors in our population because (1) no difference in vascular ICAM-1 was found in donor hearts before transplantation, (2) a decreased male/female ratio was found in the group with higher sICAM-1 concentrations, and (3) multivariate analyses showed that sICAM-1 was still an independent significant risk factor for CAD and graft failure after adjustment for these variables.
Endothelial adhesion molecules could be upregulated by ischemia and reperfusion. This is supported by the fact that 62.9% of the recipients who had sICAM-1 >308 ng/mL already had elevated sICAM-1 at 7 to 10 days after transplantation. Tissue hypoxia enhances induction of ICAM-1 in human endothelial cells, and these changes are inhibited with anti–ICAM-1 antibodies or antisense oligodeoxynucleo-tides.21 Furthermore, increased endothelial cell–surface and soluble adhesion molecules are found after ischemia and reperfusion,22 23 and blocking expression of these molecules significantly improves allograft outcome.8
Study Limitations
Basal determinations for donor sICAM-1 were not available to
determine whether donors differed in sICAM-1 before transplantation,
because hypotensive brain death induces endothelial
ICAM-1 expression.24 However,
endomyocardial biopsies obtained from all donor
hearts before transplantation showed similar immunohistochemical levels
of ICAM-1 irrespective of type of donor brain death. Because samples
were stored at -75°C for up to 10 years, we cannot exclude the
possibility of protein degradation. However, no negative correlations
were found between specimen age and either sICAM-1 values or the
likelihood of having sICAM >308 ng/mL. The unavailability of a
continuous evaluation of the status of the coronary arteries
since transplantation precludes the precise determination of the time
course for association between sICAM-1 and CAD. However, the finding of
increased sICAM-1 at 7 to 10 days after transplantation in a
significant proportion of recipients who subsequently developed CAD
suggests that ICAM-1 upregulation precedes CAD. The lack of
ultrasonographic studies in all recipients could be another limiting
factor. However, although intravascular ultrasonography is more
sensitive for detecting CAD in epicardial arteries,1 this
technique lacks accessibility to peripheral arteries, which
can be assessed by coronary angiography.10
Whatever the technique used, the measurement error would be similar in
all recipients.
Conclusions
Our findings suggest that sICAM-1 could derive from graft
endothelium. It could be released by proteolytic
cleavage by neutrophil elastase.25 This is
particularly relevant because cardiac allografts with myocardial cell
damage during the immediate posttransplant period show neutrophil
infiltration.10 The demonstration that antibodies or
antisense oligodeoxynucleotides to adhesion molecules
attenuate ischemia-reperfusion injury and subsequent
development of CAD26 and the beneficial effect of vitamin
E27 or salicylates28 on reperfusion injury
lesions by downregulating expression of adhesion molecules suggests
that antiadhesion therapies may provide a novel approach to prevent
transplant CAD. Finally, our data raise the possibility that soluble
adhesion molecules can serve as molecular markers to assess risk for
transplant CAD and graft failure. Although the clinical implications
for sICAM-1 are uncertain, closer surveillance for transplant CAD in
heart transplant recipients with elevated sICAM-1 may be warranted.
This is particularly important when we consider that these
determinations can be performed by use of a simple test that is
low-risk, inexpensive, and convenient for the patients.
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Acknowledgments |
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This research was supported by Methodist Research Institute, Clarian Health Partners; the Showalter Foundation, Indianapolis, Ind; and the American Heart Association (Midwest affiliate). The authors thank Sandra Mitchell, Alicia Currin, and Sandra Lemmon for their assistance; Roula Antonopoulos for excellent technical assistance; Beatriz Labarrere for her invaluable help; and Karen Spear, Judie Aitken, Jennifer Shaver, and Heather Richardson for editing and typing the manuscript.
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Footnotes |
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Reprint requests to Dr Carlos A. Labarrere, Methodist Research Institute, Clarian Health Partners (Methodist, Indiana University, Riley Hospitals), 1812 N Capitol Ave, Indianapolis, IN 46202.
Received March 8, 2000; revision received May 3, 2000; accepted May 4, 2000.
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References |
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1. Gao SZ, Hunt SA, Schroeder JS, et al. Early development of accelerated graft coronary artery disease: risk factors and course. J Am Coll Cardiol. 1996;28:673–679.[Abstract]
2. Mehra MR, Ventura HO, Chambers R, et al. Predictive model to assess risk for cardiac allograft vasculopathy: an intravascular ultrasound study. J Am Coll Cardiol. 1995;26:1537–1544.[Abstract]
3. Rickenbacher PR, Kemna MS, Pinto FJ, et al. Coronary artery intimal thickening in the transplanted heart: an in vivo intracoronary ultrasound study of immunologic and metabolic risk factors. Transplantation. 1996;61:46–53.[Medline] [Order article via Infotrieve]
4.
Hwang SJ, Ballantyne CM, Sharrett AR, et al.
Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in
carotid atherosclerosis and incident coronary
heart disease cases: the Atherosclerosis Risk In
Communities (ARIC) study. Circulation. 1997;96:4219–4225.
5.
Labarrere CA, Nelson DR, Faulk WP.
Endothelial activation and development of
coronary artery disease in transplanted human hearts.
JAMA. 1997;278:1169–1175.
6. Ridker PM, Hennekens CH, Roitman-Johnson B, et al. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet. 1998;351:88–92.[Medline] [Order article via Infotrieve]
7.
Fuster V, Poon M, Willerson JT. Learning from the
transgenic mouse: endothelium, adhesive molecules, and
neointimal formation. Circulation. 1998;97:16–18.
8. Suzuki J, Isobe M, Yamazaki S, et al. Inhibition of accelerated coronary atherosclerosis with short-term blockade of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in a heterotopic murine model of heart transplantation. J Heart Lung Transplant. 1997;16:1141–1148.[Medline] [Order article via Infotrieve]
9.
Labarrere CA, Pitts D, Nelson DR, et al. Vascular
tissue plasminogen activator and the
development of coronary artery disease in heart transplant
recipients. N Engl J Med. 1995;333:1111–1116.
10. Labarrere CA, Nelson DR, Faulk WP. Myocardial fibrin deposits in the first month after transplantation predict subsequent coronary artery disease and graft failure in cardiac allograft recipients. Am J Med. 1998;105:207–213.[Medline] [Order article via Infotrieve]
11. Costanzo MR, Naftel DC, Pritzker MR, et al. Heart transplant coronary artery disease detected by coronary angiography: a multi-institutional study of preoperative donor and recipient risk factors: Cardiac Transplant Research Database. J Heart Lung Transplant. 1998;17:744–753.[Medline] [Order article via Infotrieve]
12. Johnson DE, Gao SZ, Schroeder JS, et al. The spectrum of coronary artery pathologic findings in human cardiac allografts. J Heart Transplant. 1989;8:349–359.[Medline] [Order article via Infotrieve]
13.
Tanio JW, Basu CB, Albelda SM, et al. Differential
expression of the cell adhesion molecules ICAM-1, VCAM-1, and
E-selectin in normal and post-transplantation myocardium:
cell adhesion molecule expression in human cardiac allografts.
Circulation. 1994;89:1760–1768.
14. Ballantyne CM, Mainolfi EA, Young JB, et al. Relationship of increased levels of circulating intercellular adhesion molecule-1 after heart transplantation to rejection: human leukocyte antigen mismatch and survival. J Heart Lung Transplant. 1994;13:597–603.[Medline] [Order article via Infotrieve]
15. Triolo G, Triolo G, Accardo-Palumbo A, et al. IgG anti-endothelial cell antibodies (AECA) in type I diabetes mellitus: induction of adhesion molecule expression in cultured endothelial cells. Clin Exp Immunol. 1998;111:491–496.[Medline] [Order article via Infotrieve]
16. Dunn MJ, Crisp SJ, Rose ML, et al. Antiendothelial antibodies and coronary artery disease after cardiac transplantation. Lancet. 1992;339:1566–1570.[Medline] [Order article via Infotrieve]
17.
Waldman WJ, Knight DA, Huang EH. An in vitro model of T
cell activation by autologous cytomegalovirus (CMV)-infected human
adult endothelial cells: contribution of CMV-enhanced
endothelial ICAM-1. J Immunol. 1998;160:3143–3151.
18. Gulizia JM, Kandolf R, Kendall TJ, et al. Infrequency of cytomegalovirus genome in coronary arteriopathy of human heart allografts. Am J Pathol. 1995;147:461–475.[Abstract]
19.
Rohde LE, Hennekens CH, Ridker PM. Cross-sectional
study of soluble intercellular adhesion molecule-1 and
cardiovascular risk factors in apparently healthy
men. Arterioscler Thromb Vasc Biol. 1999;19:1595–1599.
20. Muller V, Szabo A, Viklicky O, et al. Sex hormones and gender-related differences: their influence on chronic renal allograft rejection. Kidney Int. 1999;55:2011–2020.[Medline] [Order article via Infotrieve]
21. Zund G, Uezono S, Stahl GL, et al. Hypoxia enhances induction of endothelial ICAM-1: role for metabolic acidosis and proteasomes. Am J Physiol. 1997;273:C1571–C1580.
22. Wyble CW, Desai TR, Clark ET, et al. Physiologic concentrations of TNF alpha and IL-1beta released from reperfused human intestine upregulate E-selectin and ICAM-1. J Surg Res. 1996;63:333–338.[Medline] [Order article via Infotrieve]
23.
Kalawski R, Bugajski P, Smielecki J, et al. Soluble
adhesion molecules in reperfusion during coronary bypass
grafting. Eur J Cardiothorac Surg. 1998;14:290–295.
24. van der Hoeven JAB, Ploeg RJ, Postema F, et al. Induction of organ dysfunction and activation of inflammatory markers in donor liver and kidney during hypotensive brain death. Transplant Proc. 1999;31:1006–1007.[Medline] [Order article via Infotrieve]
25.
Champagne B, Tremblay P, Cantin A, et al.
Proteolytic cleavage of ICAM-1 by human neutrophil elastase.
J Immunol. 1998;161:6398–6405.
26.
Poston RS, Ennen M, Pollard J, et al. Ex vivo gene
therapy prevents chronic graft vascular disease in cardiac allografts.
J Thorac Cardiovasc Surg. 1998;116:386–396.
27. Formigli L, Ibba Manneschi L, Tani A, et al. Vitamin E prevents neutrophil accumulation and attenuates tissue damage in ischemic-reperfused human skeletal muscle. Histol Histopathol. 1997;12:663–669.[Medline] [Order article via Infotrieve]
28.
Zund G, Dzus AL, Pretre R, et al.
Endothelial cell injury in cardiac surgery: salicylate
may be protective by reducing expression of endothelial
adhesion molecules. Eur J Cardiothorac Surg. 1998;13:293–297.
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 N. L. Tsakadze, U. Sen, Z. Zhao, S. D. Sithu, W. R. English, and S. E. D'Souza Signals mediating cleavage of intercellular adhesion molecule-1 Am J Physiol Cell Physiol, July 1, 2004; 287(1): C55 - C63. [Abstract] [Full Text] [PDF]
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