(Circulation. 1995;92:1693-1696.)
© 1995 American Heart Association, Inc.
Articles |
Increased Soluble Form of P-Selectin in Patients With Unstable Angina
From the Third Department of Internal Medicine (H.I., Y.T., K.I., T.U., S.M., T.I.), Kurume University School of Medicine, and the Division of Cardiology (T.N., K.S.), Sugi Hospital, Omuta, Japan.
Correspondence to Hisao Ikeda, MD, The Third Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830, Japan.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Background P-selectin in platelets and endothelial cells mediates adhesive interaction with leukocytes to form thrombi. The purpose of the present study was to investigate the plasma levels of P-selectin in patients with unstable angina and in those with stable effort angina of different pathophysiologies.
Methods and Results Plasma P-selectin levels were determined by a monoclonal antibody–based enzyme immunoassay on plasma samples taken from 12 patients with unstable angina, 11 patients with stable effort angina, and 15 healthy volunteers. Patients with unstable angina had angina at rest associated with ECG changes. In patients with unstable angina, plasma P-selectin levels within 1 hour (361±90 ng/mL) and at 3 hours (282±56 ng/mL) after angina were significantly (P<.05) higher than those in volunteers (177±31 ng/mL). Plasma P-selectin levels at 5 hours after attack (242±46 ng/mL) did not differ from those in volunteers. Although patients with stable effort angina developed angina with ST-segment depressions by treadmill exercise, their plasma P-selectin levels did not change (before, 178±45; immediately after, 186±36; and 1 hour after the exercise, 179±34 ng/mL).
Conclusions Plasma P-selectin levels after angina increased significantly in patients with unstable angina but did not in patients with stable effort angina. These findings may contribute to understanding of the pathophysiology of the acute coronary syndrome of unstable angina.
Key Words: P-selectin • angina
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Platelet aggregation and thrombus formation secondary to plaque disruption have been implicated as major pathogenic mechanisms underlying the acute coronary syndrome of unstable angina.1 2 This pathophysiology of unstable angina is different from that of effort-induced angina due to increased myocardial oxygen demand. The hypothesis of the disease process in unstable angina has been strongly supported by results of previous studies obtained in serial coronary angiographic,3 angioscopic,4 and pathological studies5 6 and in experimental studies using an animal model of coronary arterial thrombosis.7 8 The disease process of unstable angina appears to involve a transient thrombus formation mediated by a complex cascade of cellular interactions between the vascular endothelium and platelets at the atherosclerotic coronary artery.
Cell adhesion molecules play a key role in cellular interactions in
diverse disease processes, including coronary thrombosis,
atherosclerosis, restenosis after
coronary angioplasty, and reperfusion injury.9
P-selectin is a member of the selectin family and is an integral
membrane glycoprotein found in both 
-granules of
platelets10 and Weibel-Palade bodies of
endothelial cells.11 12 These molecules
contain an N-terminal lectin-like domain, an epidermal growth
factor–like domain, a variable number of consensus
repeats of a sequence found in complement regulatory proteins, a
transmembrane domain, and a short cytoplasmic tail.12
After cellular activation by agonists such as thrombin, P-selectin is
rapidly redistributed to the cell surface and binds a sialylated
carbohydrate structure expressed on neutrophils and monocytes through a
calcium-dependent lectin-like mechanism.13 14
Thus, P-selectin mediates platelet-leukocyte and
endothelial cell–leukocyte adhesive interactions.
Recent studies using a monoclonal antibody-based enzyme immunoassay
have demonstrated that the soluble form of P-selectin is present in
normal circulation.15 16 17 We previously
documented that the
soluble form of P-selectin increased markedly in patients with evolving
acute myocardial infarction.18 In the present study,
we examined the plasma level of P-selectin in patients with unstable
angina to further understand the pathophysiology of this syndrome, in
which complex interactions between the endothelium,
platelets, and neutrophils may occur to form coronary
thrombi. We also examined the plasma P-selectin in patients with stable
effort angina.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Study Patients
We analyzed the soluble form of P-selectin in the peripheral blood of 12 patients with unstable angina hospitalized in the coronary care unit: 11 men and 1 woman, 53 to 72 years old (mean, 67 years). The diagnosis of unstable angina was defined as ischemic chest pain at rest with no definite evidence of myocardial necrosis by enzymatic techniques. Transient ST-segment depression and/or T-wave inversion associated with angina was present in all patients. We studied only patients in whom blood sampling was possible after onset of chest pain. Patients who presented with ST-segment elevation or new Q waves on the ECG were excluded. Standard medications, including long-acting nitrates, calcium channel blockers, ß-blockers, and aspirin were usually started on the first day of admission if patients did not already take them. Sublingual or intravenous nitroglycerin was administered for the relief of angina attacks. No thrombolytic agents were used. Cardiac catheterization and coronary arteriography were performed by a standard technique within 1 to 2 weeks after admission. We confirmed that all patients had significant coronary artery stenosis.
We also analyzed the soluble form of P-selectin in
peripheral blood of patients with stable angina. Stable
angina was defined as effort angina without evidence of recent
deterioration or rest pain in the previous 6 months. These were 9 men
and 2 women, 48 to 77 years old (mean, 68 years). All medications as
described above were continued on the day of the treadmill exercise
test when blood samples were obtained. A treadmill test was done
according to the Bruce protocol. All patients developed typical chest
pain with horizontal ST-segment depression of 
1 mm during the
exercise test. These patients were matched to the unstable angina
patients for age, sex, and other clinical variables. A medical
history regarding previous myocardial infarction, hypertension,
smoking, and diabetes mellitus was carefully obtained in patients.
Patients with stable effort angina also underwent coronary
angiography. Plasma P-selectin levels were determined in 15 healthy
volunteers: 10 men and 5 women, 41 to 83 years old (mean, 63 years).
Written informed consent was obtained from all subjects.
Blood Sampling
Whole blood was obtained by venipuncture of
the
peripheral vein in all subjects. If a patient with unstable
angina had an anginal attack after hospitalization, a blood sample (5
mL) was collected within 1 hour and at 3 and 5 hours after the attack.
In patients with stable angina, plasma P-selectin levels were
determined before, immediately after, and 1 hour after the exercise
test. Whole blood for plasma preparation was immediately anticoagulated
with 1/10 volume of 1% EDTA-2Na. After being centrifuged at
3000g at 4°C for 10 minutes, plasma was frozen at -80°C
until assay.
Enzyme Immunoassay for Soluble Form of P-Selectin
The plasma
level of P-selectin was determined according to a
previously described method15 16 with a P-selectin
kit
(Takara Biomedicals). Briefly, 100 µL of plasma was added to 96-well
plates coated with the first monoclonal antibody (WGA-1) and then
blocked with 1% BSA. A volume of 100 µL of standard P-selectin (0,
10, 20, 40, 80, 160, and 320 ng/mL) or blood sample was added to each
well. The plates were incubated for 1 hour at 37°C and washed with
PBS. We then added 100 µL of solution of the second monoclonal
antibody (PL7-6) labeled with horseradish peroxidase to each well and
incubated the plate for 1 hour at 37°C. After PBS washing, 100 µL
of 5.5 mmol/L o-phenylenediamine · 2HCl
solution was added as a substrate, and the mixture was left for 15
minutes at room temperature. The enzyme reaction was stopped by the
addition of 100 µL of 1N H2SO4, and
absorbance at 492 nm was measured in a microplate reader.
Statistics
Values are presented as mean±SD. The
clinical
characteristics of the two study groups described in the
Table
were compared by unpaired Student's t
test, 
2 test, or Fisher's exact probability
test. The values of plasma P-selectin levels obtained at different time
periods were compared by repeated-measures ANOVA with the
Scheffé test. Differences were considered statistically
significant at P<.05.
|
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Clinical Characteristics
The clinical characteristics of patients with unstable and stable angina were similar for age, sex distribution, and major risk factors (Table
). A history of previous myocardial infarction was not
noted in
patients in the unstable angina group, but one patient in the stable
angina group had such a history. The angiographic characteristics were
similar between the two groups. Patients with unstable and stable
angina did not differ in the use of ß-blockers (33% versus
45%), long-acting nitrates (83% versus 82%), calcium channel
blockers (92% versus 100%), and aspirin (100% versus 100%). There
were no significant differences in the frequency of smoking or in serum
cholesterol levels between the patients with unstable
angina, those with stable angina, and the healthy volunteers.
Plasma P-Selectin Levels in Unstable Angina
Fig
1A shows the plasma P-selectin levels in 15
healthy volunteers and in 12 patients with unstable angina. Plasma
P-selectin levels in volunteers were 177±31 ng/mL. Plasma P-selectin
levels in patients with unstable angina within 1 hour and at 3 and 5
hours after onset of anginal attack were 361±90, 282±56, and
242±46
ng/mL, respectively. Plasma P-selectin levels within 1 hour and at 3
hours after anginal attack were both significantly higher than those in
control subjects (P<.05). Plasma P-selectin levels at 5
hours after anginal attack were significantly (P<.05) lower
than those at 1 hour and did not differ from those in control
subjects.
|
P<.05 compared with those within 1 hour. B, Bar graph
showing plasma concentration of P-selectin before and after exercise
stress test in patients with stable effort angina. Although
exercise-induced ischemia was observed in all patients
during the exercise test, there were no significant increases in plasma
P-selectin levels.
Plasma P-Selectin Levels Before and After Exercise Test in Patients
With Stable Angina
Fig 1B shows the plasma P-selectin
levels before and after
treadmill exercise test in 11 patients with stable angina. Plasma
P-selectin levels before, immediately after, and 1 hour after exercise
test were 178±45, 186±36, and 179±34 ng/mL, respectively.
Plasma
P-selectin levels before exercise test did not differ from those in
control subjects. Plasma P-selectin levels did not change with exercise
test (P=NS).
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
In the present study, plasma P-selectin levels after anginal attacks were significantly elevated in patients with unstable angina compared with those in patients with stable effort angina and in control subjects. The levels decreased toward the control value within several hours after the cessation of rest angina. In contrast, patients with stable effort angina did not show any change in plasma P-selectin levels after exercise test, although these patients clearly showed evidence of exercise-induced ischemia, with typical ischemic chest pain and horizontal ST-segment depressions. Thus, the present findings may suggest that the pathophysiology of unstable angina is closely related to coronary arterial thrombi through the cellular interactions among platelets, leukocytes, and endothelial cells.
In the present study, we measured plasma P-selectin using the sandwich enzyme immunoassay with two different anti–P-selectin murine monoclonal antibodies. The specificity of these monoclonal antibodies for P-selectin was previously demonstrated by Katayama et al,15 who demonstrated that these monoclonal antibodies bound to different antigenic epitopes on human P-selectin in a noncompetitive manner and showed no cross-reaction with human E-selectin and L-selectin. These investigators confirmed that the P-selectin levels in platelet-poor plasma were similar to the P-selectin levels in whole blood obtained by standard blood sampling procedures, indicating that the P-selectin detected in plasma is an in vivo product rather than the result of in vitro platelet aggregation.16 The plasma level obtained in healthy subjects was 177±31 ng/mL, which was similar to those reported by Dunlop et al17 (175±63 in women and 251±43 ng/mL in men), those reported by Katayama et al16 (121±84 ng/mL), and those reported by us18 (178±44 ng/mL), indicating stable and reliable measurements of P-selectin by our method.
We measured the plasma level of P-selectin on the assumption that plasma contains only water-soluble molecules and that immunochemical reaction with monoclonal antibody is specific for the soluble molecule. However, analysis of the complementary DNA demonstrated the possible presence of a soluble form of P-selectin that possesses a deleted transmembrane segment derived from alternative splicing of mRNA.19 Thus, it is possible that the P-selectin detected in the present study is a mixture of a soluble form and a membrane form produced by alternative splicing of mRNA.
The acute inflammatory reaction may occur at the site of atherosclerotic coronary obstruction in acute coronary syndromes.20 In the present study, P-selectin, an increase of which indicates inflammation, was elevated after anginal attacks in patients with unstable angina. Although it is difficult to determine the exact source of plasma P-selectin in the present study, there are several possibilities to account for increased levels of plasma P-selectin in unstable angina. It is well known that thrombin is the principal mediator of thrombus formation at the site of vascular injury in vivo.21 Thrombin can rapidly induce the expression of a membrane form of P-selectin on the surface of platelet and endothelial cell.10 13 A recent study by Palabrica et al22 demonstrated that the presence of leukocytes in thrombi is mediated by P-selectin in vivo and that these leukocytes promote fibrin deposition. These findings indicate that the membrane form of P-selectin is an important adhesion molecule on platelets in mediating platelet-leukocyte binding in vivo. Once platelets and leukocytes are thus activated, vasoactive substances such as thromboxane A2 and leukotrienes are released and further induce platelet aggregation and vasoconstriction. The present data, therefore, suggest that platelets and/or endothelial cells might be activated through interactions with leukocytes during anginal attacks in patients with unstable angina. In contrast to the membrane form of P-selectin, a soluble form of P-selectin is shown to prevent leukocyte ß2-integrin adhesion, suggesting that this form may serve to limit thrombosis and inflammatory reactions.23 Thus, the increased levels of plasma P-selectin in unstable angina observed in the present study may play an important role in limiting coronary thrombosis.
The present study demonstrated no significant changes in plasma P-selectin levels after exercise-induced anginal attacks in patients with stable effort angina, even though these patients clearly showed evidence of exercise-induced ischemia. This observation suggested that plasma increases in P-selectin did not result from exercise-induced ischemia and that increased plasma P-selectin in unstable angina might be related to a transient thrombus formation through interactions between leukocytes and platelets and/or endothelial cells.
In the present study, patients with unstable angina had significant increases in plasma P-selectin levels, which gradually decayed to normal levels several hours after the cessation of rest angina. The concentration range and the time course of the elevations in plasma P-selectin levels in patients with unstable angina were different from those we reported previously in patients with acute myocardial infarction.18 Plasma P-selectin levels on day 1 in patients with acute myocardial infarction ranged from 320 to 1458 ng/mL, twofold to threefold higher than those in patients with unstable angina. Thus, these observations may suggest the different severities of coronary artery thrombosis between unstable angina and acute myocardial infarction.
The present study demonstrates for the first time, to the best of our knowledge, that plasma P-selectin levels increase significantly after anginal attacks in patients with unstable angina. Since mRNA encoding the soluble form exists in both platelets19 and endothelium,12 measurements of plasma P-selectin may help us to understand the pathophysiology of unstable angina and may be clinically useful as a new molecular marker of platelet aggregation and thrombus formation in acute coronary syndromes.
|
Acknowledgments |
|---|
This work was supported in part by a grant-in-aid for Scientific Research (20217938) from the Ministry of Education, Science, and Culture, Tokyo, Japan.
Received May 4, 1995; revision received July 11, 1995; accepted July 26, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Hirsh PD, Hillis LD, Campbell WB, Firth BG, Willerson JT. Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med. 1981;304:685-691. [Abstract]
2.
Fuster V, Badimon L, Cohen M, Ambrose JA, Badimon JJ,
Chesebro JH. Insights into the pathogenesis of acute
ischemic syndromes. Circulation. 1988;77:1213-1220.
3.
The TIMI IIIA Investigators. Early effects of
tissue-type plasminogen activator added to
conventional therapy on the culprit lesion in patients presenting
with ischemic cardiac pain at rest: results of the
Thrombolysis in Myocardial Ischemia (TIMI IIIA)
Trial. Circulation. 1993;87:38-52.
4. Mizuno K, Satomura K, Miyamoto A, Arakawa K, Shibuya T, Arai T, Kurita A, Nakamura H, Ambrose JA. Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes. N Engl J Med. 1992;326:287-291. [Abstract]
5.
Falk E. Unstable angina with fatal outcome:
dynamic coronary thrombosis leading to infarction and/or sudden
death: autopsy evidence of recurrent mural thrombosis with
peripheral embolization culminating in total vascular
occlusion. Circulation. 1985;71:699-708.
6.
Davies MJ, Thomas AC, Knapman PA, Hangartner JR.
Intramyocardial platelet aggregation in patients with
unstable angina suffering sudden ischemic cardiac
death. Circulation. 1986;73:418-427.
7.
Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM.
Specific platelet mediators and unstable coronary
artery lesions: experimental evidence and potential clinical
implications. Circulation. 1989;80:198-205.
8. Ikeda H, Koga Y, Kuwano K, Nakayama H, Ueno T, Yoshida N, Adachi K, Park IS, Toshima H. Cyclic flow variations in a conscious dog model of coronary artery stenoses and endothelial injury correlate with acute ischemic heart disease syndromes in humans. J Am Coll Cardiol. 1993;21:1008-1017. [Abstract]
9. Jang Y, Lincoff AM, Plow EF, Topol EJ. Cell adhesion molecules in coronary artery disease. J Am Coll Cardiol. 1994;24:1591-1601. [Abstract]
10.
Steinberg PE, McEver RP, Shuman MA, Jacques YV, Bainton
DF. A platelet alpha-granule membrane protein (GMP-140)
is expressed on the plasma membrane after activation.
J Cell Biol. 1985;101:880-886.
11. McEver RP, Beckstead JH, Moore KL, Marshall-Carlton L, Bainton DF. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest. 1989;84:92-99.
12. Johnston GI, Cook RG, McEver RP. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989;56:1033-1044. [Medline] [Order article via Infotrieve]
13. Geng JG, Bevilacqua MP, Moore KL, McIntyre TM, Prescott SM, Kim JM, Bliss GA, Zimmerman GA, McEver RP. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990;343:757-760. [Medline] [Order article via Infotrieve]
14.
Polley MJ, Phillips ML, Wayner E, Nudelman E, Singhal
AK, Hakomori S, Paulson JC. CD62 and endothelial
cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same
carbohydrate ligand, sialyl-Lewis x. Proc Natl Acad Sci
U S A. 1991;88:6224-6228.
15. Katayama M, Handa M, Ambo H, Araki Y, Hirai S, Kato I, Kawai I, Watanabe K, Ikeda Y. A monoclonal antibody-based enzyme immunoassay for human GMP-140/P-selectin. J Immunol Methods. 1992;153:41-48. [Medline] [Order article via Infotrieve]
16. Katayama M, Handa M, Araki Y, Anbo H, Kawai Y, Watanabe K, Ikeda Y. Soluble P-selectin is present in normal circulation and its plasma level is elevated in patients with thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. Br J Haematol. 1993;84:702-710. [Medline] [Order article via Infotrieve]
17.
Dunlop LC, Skinner MP, Bendall LJ, Favaloro EJ,
Castaldi PA, Gorman JJ, Gamble JR, Vadas MA, Berndt MC.
Characterization of GMP-140 (P-selectin) as a circulating
plasma protein. J Exp Med. 1992;175:1147-1150.
18. Ikeda H, Nakayama H, Oda T, Kuwano K, Muraishi A, Sugi K, Koga Y, Toshima H. Soluble form of P-selectin in patients with acute myocardial infarction. Coron Artery Dis. 1994;5:515-518. [Medline] [Order article via Infotrieve]
19.
Johnston GI, Bliss GA, Newman PJ, McEver RP.
Structure of the human gene encoding granule membrane
protein-140, a member of the selectin family of adhesion receptors for
leukocytes. J Biol Chem. 1990;265:21381-21385.
20.
Entman ML, Ballantyne CM. Inflammation in acute
coronary syndromes. Circulation. 1993;88:800-803.
21. Harker LA, Hanson SR, Runge MS. Thrombin hypothesis of thrombus generation and vascular lesion formation. Am J Cardiol. 1995;75:12B-17B. [Medline] [Order article via Infotrieve]
22. Palabrica T, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu YM, Sajer SA, Furie B. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature. 1992;359:848-851.[Medline] [Order article via Infotrieve]
23.
Gamble JR, Skinner MP, Berndt MC, Vadas MA.
Prevention of activated neutrophil adhesion to
endothelium by soluble adhesion protein
GMP-140. Science. 1990;249:414-417.
This article has been cited by other articles:
 |
|
 |
|
  C. Vlachopoulos, P. Xaplanteris, N. Alexopoulos, K. Aznaouridis, C. Vasiliadou, K. Baou, E. Stefanadi, and C. Stefanadis Divergent Effects of Laughter and Mental Stress on Arterial Stiffness and Central Hemodynamics Psychosom Med, May 1, 2009; 71(4): 446 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ay, L. V. Jungbauer, T. Sailer, T. Tengler, S. Koder, A. Kaider, S. Panzer, P. Quehenberger, I. Pabinger, and C. Mannhalter High Concentrations of Soluble P-Selectin Are Associated with Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant Clin. Chem., July 1, 2007; 53(7): 1235 - 1243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Galkina and K. Ley Double Jeopardy: How Soluble P-Selectin Activates Leukocytes in Peripheral Arterial Occlusive Disease Circ. Res., January 6, 2006; 98(1): 12 - 14. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Garcia-Touchard, T. D. Henry, G. Sangiorgi, L. G. Spagnoli, A. Mauriello, C. Conover, and R. S. Schwartz Extracellular Proteases in Atherosclerosis and Restenosis Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1119 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. del Conde, F. Nabi, R. Tonda, P. Thiagarajan, J. A. Lopez, and N. S. Kleiman Effect of P-Selectin on Phosphatidylserine Exposure and Surface-Dependent Thrombin Generation on Monocytes Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 1065 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Frossard, I. Fuchs, J. M. Leitner, K. Hsieh, M. Vlcek, H. Losert, H. Domanovits, W. Schreiber, A. N. Laggner, and B. Jilma Platelet Function Predicts Myocardial Damage in Patients With Acute Myocardial Infarction Circulation, September 14, 2004; 110(11): 1392 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Vinten-Johansen Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury Cardiovasc Res, February 15, 2004; 61(3): 481 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Blann, S. K. Nadar, and G. Y.H. Lip The adhesion molecule P-selectin and cardiovascular disease Eur. Heart J., December 2, 2003; 24(24): 2166 - 2179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Frazier Novel Predictors of Acute Coronary Syndrome Outcomes Biol Res Nurs, July 1, 2003; 5(1): 30 - 36. [Abstract] [PDF]
|
|
|
|
 |
|
 P. C. Burger and D. D. Wagner Platelet P-selectin facilitates atherosclerotic lesion development Blood, April 1, 2003; 101(7): 2661 - 2666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.W. Eikelboom, J.I. Weitz, A. Budaj, F. Zhao, I. Copland, P. Maciejewski, M. Johnston, and S. Yusuf Clopidogrel does not suppress blood markers of coagulation activation in aspirin-treated patients with non-ST-elevation acute coronary syndromes Eur. Heart J., November 2, 2002; 23(22): 1771 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.T. Mulvihill, B. Foley, P. Crean, and M. Walsh Prediction of cardiovascular risk using soluble cell adhesion molecules Eur. Heart J., October 2, 2002; 23(20): 1569 - 1574. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mirabet, D. Garcia-Dorado, J. Inserte, J. A. Barrabes, R.-M. Lidon, B. Soriano, M. Azevedo, F. Padilla, L. Agullo, M. Ruiz-Meana, et al. Platelets activated by transient coronary occlusion exacerbate ischemia-reperfusion injury in rat hearts Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1134 - H1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-A. Tregouet, S. Barbaux, S. Escolano, N. Tahri, J.-L. Golmard, L. Tiret, and F. Cambien Specific haplotypes of the P-selectin gene are associated with myocardial infarction Hum. Mol. Genet., August 15, 2002; 11(17): 2015 - 2023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Devaraj, A. V. C. Chan Jr., and I. Jialal {alpha}-Tocopherol Supplementation Decreases Plasminogen Activator Inhibitor-1 and P-Selectin Levels in Type 2 Diabetic Patients Diabetes Care, March 1, 2002; 25(3): 524 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N T Mulvihill and J B Foley Inflammation in acute coronary syndromes Heart, March 1, 2002; 87(3): 201 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F Andreotti, I Porto, F Crea, and A Maseri Inflammatory gene polymorphisms and ischaemic heart disease: review of population association studies Heart, February 1, 2002; 87(2): 107 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C D Garlichs, S Eskafi, D Raaz, A Schmidt, J Ludwig, M Herrmann, L Klinghammer, W G Daniel, and A Schmeisser Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets Heart, December 1, 2001; 86(6): 649 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Poredos State-of-the-Art Review: Endothelial Dysfunction in the Pathogenesis of Atherosclerosis Clinical and Applied Thrombosis/Hemostasis, October 1, 2001; 7(4): 276 - 280. [Abstract] [PDF]
|
|
|
|
|
|
S. C. Barbaux, S. Blankenberg, H. J. Rupprecht, C. Francomme, C. Bickel, G. Hafner, V. Nicaud, J. Meyer, F. Cambien, and L. Tiret Association Between P-Selectin Gene Polymorphisms and Soluble P-Selectin Levels and Their Relation to Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., October 1, 2001; 21(10): 1668 - 1673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ridker, J. E. Buring, and N. Rifai Soluble P-Selectin and the Risk of Future Cardiovascular Events Circulation, January 30, 2001; 103(4): 491 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. André, D. Hartwell, I. Hrachovinová, S. Saffaripour, and D. D. Wagner Pro-coagulant state resulting from high levels of soluble P-selectin in blood PNAS, November 22, 2000; (2000) 250475997. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. T. Mulvihill, J. B. Foley, R. Murphy, P. Crean, and M. Walsh Evidence of prolonged inflammation in unstable angina and non-Q wave myocardial infarction J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1210 - 1216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Amin, S. Ahmad, J. M. Walenga, D. A. Hoppensteadt, H. Leitz, and J. Fareed Soluble P-Selectin in Human Plasma: Effect of Anticoagulant Matrix and its Levels in Patients With Cardiovascular Disorders Clinical and Applied Thrombosis/Hemostasis, April 1, 2000; 6(2): 71 - 76. [Abstract] [PDF]
|
|
|
|
|
|
P. Aukrust, F. Muller, T. Ueland, T. Berget, E. Aaser, A. Brunsvig, N. O. Solum, K. Forfang, S. S. Froland, and L. Gullestad Enhanced Levels of Soluble and Membrane-Bound CD40 Ligand in Patients With Unstable Angina : Possible Reflection of T Lymphocyte and Platelet Involvement in the Pathogenesis of Acute Coronary Syndromes Circulation, August 10, 1999; 100(6): 614 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Hollander, M. R. Muttreja, M. R. Dalesandro, and F. S. Shofer Risk stratification of emergency department patients with acute coronary syndromes using P-Selectin J. Am. Coll. Cardiol., July 1, 1999; 34(1): 95 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H.B. Wu, F. S. Apple, W. B. Gibler, R. L. Jesse, M. M. Warshaw, and R. Valdes Jr. National Academy of Clinical Biochemistry Standards of Laboratory Practice: Recommendations for the Use of Cardiac Markers in Coronary Artery Diseases Clin. Chem., July 1, 1999; 45(7): 1104 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Jones, W. G. Girod, A. J. Palazzo, D. N. Granger, M. B. Grisham, D. Jourd'Heuil, P. L. Huang, and D. J. Lefer Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1567 - H1573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ikeda, T. Ueyama, T. Murohara, H. Yasukawa, N. Haramaki, H. Eguchi, A. Katoh, Y. Takajo, I. Onitsuka, T. Ueno, et al. Adhesive Interaction Between P-Selectin and Sialyl Lewisx Plays an Important Role in Recurrent Coronary Arterial Thrombosis in Dogs Arterioscler. Thromb. Vasc. Biol., April 1, 1999; 19(4): 1083 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Eguchi, H. Ikeda, T. Murohara, H. Yasukawa, N. Haramaki, S. Sakisaka, and T. Imaizumi Endothelial Injuries of Coronary Arteries Distal to Thrombotic Sites : Role of Adhesive Interaction Between Endothelial P-Selectin and Leukocyte Sialyl LewisX Circ. Res., March 19, 1999; 84(5): 525 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Ault, C. P. Cannon, J. Mitchell, J. McCahan, R. P. Tracy, W. F. Novotny, J. D. Reimann, and E. Braunwald Platelet activation in patients after an acute coronary syndrome: results from the TIMI-12 trial J. Am. Coll. Cardiol., March 1, 1999; 33(3): 634 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Palazzo, S. P. Jones, W. G. Girod, D. C. Anderson, D. N. Granger, and D. J. Lefer Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice Am J Physiol Heart Circ Physiol, December 1, 1998; 275(6): H2300 - H2307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Aoki and H. Tomoda Plasma Soluble P-Selectin in Acute Myocardial Infarction: Effects of Coronary Recanalization Therapy Angiology, September 1, 1998; 49(9): 807 - 813. [Abstract] [PDF]
|
|
|
|
|
|
G S Hillis and A D Flapan Cell adhesion molecules in cardiovascular disease: a clinical perspective Heart, May 1, 1998; 79(5): 429 - 431. [Full Text]
|
|
|
|
|
|
G. Davi, M. Romano, A. Mezzetti, A. Procopio, S. Iacobelli, T. Antidormi, T. Bucciarelli, P. Alessandrini, F. Cuccurullo, and G. B. Bon Increased Levels of Soluble P-Selectin in Hypercholesterolemic Patients Circulation, March 17, 1998; 97(10): 953 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster, M. Poon, and J. T. Willerson Learning From the Transgenic Mouse : Endothelium, Adhesive Molecules, and Neointimal Formation Circulation, January 13, 1998; 97(1): 16 - 18. [Full Text] [PDF]
|
|
|
|
|
|
R. P. Tracy, B. M. Psaty, E. Macy, E. G. Bovill, M. Cushman, E. S. Cornell, and L. H. Kuller Lifetime Smoking Exposure Affects the Association of C-Reactive Protein with Cardiovascular Disease Risk Factors and Subclinical Disease in Healthy Elderly Subjects Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 2167 - 2176. [Abstract] [Full Text]
|
|
|
|
|
|
T. Ueyama, H. Ikeda, N. Haramaki, K. Kuwano, and T. Imaizumi Effects of Monoclonal Antibody to P-Selectin and Analogue of Sialyl Lewis X on Cyclic Flow Variations in Stenosed and Endothelium-Injured Canine Coronary Arteries Circulation, March 18, 1997; 95(6): 1554 - 1559. [Abstract] [Full Text]
|
|
|
|
|
|
J.-W. Gu, D. Santiago, Y. Olowe, and J. Weinberger Basic Fibroblast Growth Factor as a Biochemical Marker of Exercise-Induced Ischemia Circulation, March 4, 1997; 95(5): 1165 - 1168. [Abstract] [Full Text]
|
|
|
|
|
|
K. Peter, P. Nawroth, C. Conradt, T. Nordt, T. Weiss, M. Boehme, A. Wunsch, J. Allenberg, W. Kubler, and C. Bode Circulating Vascular Cell Adhesion Molecule-1 Correlates With the Extent of Human Atherosclerosis in Contrast to Circulating Intercellular Adhesion Molecule-1, E-Selectin, P-Selectin, and Thrombomodulin Arterioscler. Thromb. Vasc. Biol., March 1, 1997; 17(3): 505 - 512. [Abstract] [Full Text]
|
|
|
|
|
|
G. Liuzzo, L. M. Biasucci, A. G. Rebuzzi, J. R. Gallimore, G. Caligiuri, G. A. Lanza, G. Quaranta, C. Monaco, M. B. Pepys, and A. Maseri Plasma Protein Acute-Phase Response in Unstable Angina Is Not Induced by Ischemic Injury Circulation, November 15, 1996; 94(10): 2373 - 2380. [Abstract] [Full Text]
|
|
|
|
|
|
B. Pitt Risk Stratification in Patients With Unstable Angina : `Deja Vu All Over Again'? Circulation, May 1, 1996; 93(9): 1618 - 1620. [Full Text]
|
|
|
|
|
|
P. Andre, D. Hartwell, I. Hrachovinova, S. Saffaripour, and D. D. Wagner Pro-coagulant state resulting from high levels of soluble P-selectin in blood PNAS, December 5, 2000; 97(25): 13835 - 13840. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||