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Microparticles (MPs) and miRNAs have been shown to play important roles in coronary artery disease (CAD) by monitoring endothelial dysfunction. The present study aims to investigate the diagnostic value of endothelial MPs (EMPs) and miRNAs ( miR-92a or miR-23a ) as biomarkers in distinguishing patients with acute myocardial infarction (AMI) from those with CAD. Plasma samples from 37 patients with AMI, 42 patients with stable CAD (SCAD), and 35 healthy adults were collected for investigation in the present study. The numbers of CD31+/CD42b- MPs, CD31+/CD42b+ MPs, and CD31-/CD42b- MPs were measured by flow cytometry and the levels of miR-92a and miR-23a were analyzed using reverse transcription-quantitative PCR. Moreover, cardiac troponin I (cTnI) expression was detected by ELISA to serve as a routine diagnostic parameter. The number of CD31+/CD42b- was higher in AMI group than those in SCAD and healthy groups. Besides, the expression of miR-92a was higher in AMI group compared with two other groups. Furthermore, evidence showed that there was a positive correlation between the levels of CD31+/CD42b- MPs and miR-92a Finally, the receiver operating characteristic (ROC) curve revealed that the area value under the curve of CD31+/CD42b- MPs, miR-92a and cTnI was 0.893, 0.888, and 0.912 respectively. CD31+/CD42b- MPs and miR-92a might have great potential to provide diagnostic value for AMI and could probably regulate the endothelial dysfunction in AMI patients., (© 2017 The Author(s).)

We studied relationship between markers of endothelial dysfunction and multifocal atherosclerosis and adverse coronary events in 82 patients with non-ST segment elevation acute coronary syndrome (NSTEACS). Eighteen patients (21.9%) had adverse events during one year of observation. Patients with adverse coronary events had impaired vasodilatory, vasoconstrictive, and adhesive endothelial function. Predictors of unfavorable prognosis in NSTEACS were signs of impaired endothelium-dependent vasodilation during test with reactive hyperemia, high soluble platelet selectin and endothelin-1 levels on day 10 of the disease. Endothelin-1 and soluble platelet-endothelial cell adhesion molecule-1 had greatest predictive power relative to development of non-fatal myocardial infarction.

Objectives: Microparticles (MP) are small membrane vesicles, released from activated, damaged and apoptotic endothelial cells (EMP) or platelets (PMP) that may actively modulate inflammation, coagulation and vascular function. We tested the hypothesis that the number of circulating EMP or PMP in acute myocardial infarction correlates with the myocardium at risk (MaR) and infarct size (IS)., Methods: EMP were quantified in plasma samples of 36 patients (age: 63±10 years) with first time ST-elevation myocardial infarction (STEMI) using flow cytometry. EMP were defined as CD31(+)/CD42(-) MP and CD144(+) MP and PMP as CD31(+)/CD42(+) MP. MaR and IS was determined by cardiovascular magnetic resonance imaging one week after the index event., Results: Plasma levels of CD31(+)/CD42(-) EMP were 251.0±178.8/μl and CD144(+) 106.3±33.7/μl. PMP levels were 579.2±631.8/μl. MaR was 31.0±11.2% of the left ventricle and IS was 11.4±7.1% of the left ventricle. Patients with STEMI in the left anterior descending artery had higher levels of CD31(+)/CD42(-) EMP and PMP than those with other infarct-related arteries (p<0.05). The numbers of CD31(+)/CD42(-) EMP and PMP correlated to MaR, but not to IS., Conclusions: Circulating EMP and PMP correlate to the size of MaR in patients with STEMI suggesting that they reflect the severity of the endothelial injury and platelet activation during myocardial ischemia., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: endothelial damage and dysfunction play a crucial role in the pathophysiology of coronary artery disease (CAD). The quantification of circulating endothelial cells (CEC) in the peripheral blood is a novel method for assessing endothelial damage., Aim: to evaluate the possible diagnostic use of single quantification of CEC in peripheral blood by flow cytometry in patients with CAD., Methods: we examined 48 patients with CAD, including 23 patients with acute myocardial infarction (AMI) and 25 patients with stable angina (SA). The control group consisted of 20 healthy subjects without symptoms of CAD. The CEC count was evaluated by flow cytometry using antibodies against CD31, CD146, and CD45. Plasma biochemical markers of endothelial damage (von Willebrand Factor [vWF], thrombomodulin [TM]) were measured by ELISA. Serum concentrations of troponin I (TnI) and lipid parameters were also included in the statistical analysis., Results: A significant increase in the CEC count was found in patients with AMI compared to the control group (p < 0.05) and SA patients (p < 0.05). However, no difference was found in the CEC count between patients with SA and the control group. Increased vWF activity was found in both groups of CAD patients compared to the control group (AMI: p < 0.001, SA: p , 0.01), and vWF activity was significantly higher in AMI patients compared to SA patients (p < 0.001). Thrombomodulin concentration did not differ significantly between any patient groups and the control group. The CEC count correlated positively with vWF activity (r = 0.3852, p < 0.05) and the atherogenic index TC/HDL-C (r = 0.3844, p < 0.05) in all patients with CAD (AMI + SA). The sensitivity of CEC count for the diagnosis of an acute coronary syndrome was lower than that of TnI level on admission (39% vs 69%)., Conclusions: we confirmed that CEC count in peripheral blood can be determined by flow cytometry in CAD patients with both AMI and SA. The CEC count in AMI was increased in comparison to healthy subjects and SA patients in one third of all cases. To determine whether CEC count could be used to improve the diagnosis of an acute coronary syndrome in patients with CAD, additional studies in larger patient groups would be required.

Background: The relationships among the circulating levels of endothelial progenitor cells (EPC), stromal cell-derived factor (SDF)-1alpha, interleukin (IL)-10 and outcome were examined in patients with ST-segment elevation acute myocardial infarction (ST-se AMI) undergoing primary coronary angioplasty., Methods and Results: Circulating levels of IL-10, SDF-1alpha, and EPCs [defined by staining markers: CD31/CD34 (E(1)) and KDR/CD34 (E(2))] were examined by ELISA and flow cytometry, respectively. The IL-10 level was higher, whereas the circulating level of EPCs (E(1-2)) was lower (all P<0.05) in AMI patients than in normal subjects. Additionally, the SDF-1alpha level was significantly and independently predictive of an increased level of circulating EPCs (E(1-2)) (P<0.0001). Furthermore, patients with a high SDF-1alpha level (>1,500 pg/ml) had lower left ventricular performance, higher Killip score (defined as >or=3), and increased 30-day mortality than those with low SDF-1alpha level (or=3 or 30-day mortality) (P<0.01)., Conclusions: The serum SDF-1alpha level is independently predictive of an increased level of circulating EPCs (E(1-2)). E(2) and IL-10 are major independent predictors of 30-day MACO in ST-se AMI patients undergoing primary coronary angioplasty.

Objective: To investigate the association of single nucleotide polymorphism (SNP) and its haplotypes of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene with susceptibility to acute myocardial infarction (AMI), and to analyze association the serum levels and genotypes of PECAM-1 with AMI., Methods: Three SNPs of PECAM-1 gene Leu125Val, Asn563Ser and Gly670Arg were analyzed in 180 patients with AMI and 200 age and sex matched controls, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy, and the serum level of PECAM-1 was determined by enzyme linked immunosorbent assay (ELISA). Frequency of haplotypes and linkage disequilibrium of PECAM-1 gene in different groups were analyzed by SHEsis programs., Results: The distributions of PECAM-1 gene Asn563Ser and Gly670Arg polymorphisms were not different between AMI and control group (P>0.05), but the PECAM-1 gene Leu125Val polymorphism was significantly different (P<0.05). The relative risk suffered from AMI of Val allele was 1.480 folds of the Leu allele carriers [odds ratio (OR)=1.480, 95% confidence interval (CI): 1.111-1.972, P=0.007]; the serum level of PECAM-1 Val allele carriers was significantly higher than that of noncarriers (P<0.01). With the results of the genotyping analyses, PECAM-1 gene Leu125Val, Asn563Ser and Gly670Arg polymorphisms showed strong linkage disequilibrium, and the Val-Ser-Arg haplotype was associated with a significantly increased risk of AMI as compared with the controls (OR=1.489, 95%CI: 1.118-1.984, P=0.006)., Conclusion: PECAM-1 gene Leu125Val polymorphism and its Val-Ser-Arg haplotype are associated with AMI, Val allele is an important genetic susceptibility gene for AMI. The PECAM-1 Val allele carriers may have a higher risk by enhancing the PECAM-1 expression in the pathogenesis of AMI.

In order to investigate the association of G+1688A (Ser563Asn) polymorphism of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene with myocardial infarction (MI) in the Chinese Han population, the G+1688A polymorphism in PECAM-1 gene was detected by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method among 502 subjects, including 218 patients with MI and 284 controls. The results showed that there was significant difference in AA frequencies of genotype G+1688A polymorphism between case and control groups (39% vs 24%, P<0.001). A similar trend was observed on the allele frequencies (A/G: 62% vs 49%, P<0.001). Among the subjects with high serum total cholesterol level or high systolic blood pressure level, the variant AA genotype was associated with high risk of MI (adjusted OR, 2.13; 95% CI, 1.08-4.41 and adjusted OR, 2.53; 95%CI, 1.63-3.63). The single nucleotide polymorphism (SNP) at position +1688 in the exon 8 of PECAM-1 gene was associated with MI and the allele A might be a risk factor for MI in the Chinese Han population.

Atherosclerosis is a complex disease involved in major fatal events such as myocardial infarction and stroke. It is the result of interactions between metabolic, dietetic and environmental risk factors acting on a genetic background that could result in endothelial susceptibility. Our aim was to determine the patterns of expression of adhesion molecules and whether phosphatidylserine is translocated to the cell surface of human umbilical vein endothelial cells (HUVECs) isolated from healthy newborns born to parents with a strong family history of myocardial infarction under TNF-alpha or oxLDL stimulated conditions. Compared to control HUVECs, experimental cords showed: (a) a four-fold increase in VCAM-1 expression under basal conditions, which showed no change after stimulation with the pro-atherogenic factors; (b) a two-fold increase in basal P-selectin expression that reached a 10-fold increase with any of the pro-atherogenic factors; (c) a basal ICAM-1 expression similar to P-selectin that was not modified by the pro-atherogenic molecules; (d) a similar PECAM-1 expression. Unexpectedly, phospathidylserine expression in experimental cord HUVECs was significantly increased (211 817 versus 3354 TFU) but was not associated to apoptotic death as the percentage of dead cells induced by TNF-alpha treatment was very low (0.55 versus 9.87% in control HUVECs). The latter result was corroborated by TUNEL staining. T cell adherence to HUVECs was highly up-regulated in the genetically predisposed samples. The analysis of nonpooled HUVECs, from newborns to family predisposed myocardial-infarction individuals, might represent a useful strategy to identify phenotypical and functional alterations, and hopefully, to take early preventive actions.

The pathogenesis of arterial thrombotic disease involves multiple genetic and environmental factors related to atherosclerosis and thrombosis. The endothelium is a monolayer of polygonal cells that extend continuously over the luminal surface of the entire vasculature. Injury to the endothelium leads to dysfunction. The causes of injury include lipids, immune complexes, microorganisms, smoking, hypertension, aging, diabetes mellitus and trauma. Studies have been done to evaluate the role of different adhesion molecules on the endothelial membrane in the pathogenesis of atherosclerosis. These molecules are intercellular adhesion molecule type-1 (ICAM-1), vascular cell adhesion molecule type-1 (VCAM-1), platelet/endothelial cell adhesion molecule-1 (PECAM-1), soluble P-selectin (sP-selectin) and soluble E-selectin (sE-selectin). One-hundred and twenty patients of myocardial infarction (age below 40 years) were recruited from the out-patients department of Department of Cardiology, KEM Hospital, Mumbai. All the patients were recruited 8-10 weeks after stabilization after MI. We estimated the levels of sP-selectin, sE-selectin, sPECAM-1 and serum homocysteine. Healthy age and sex-matched controls and family controls were also recruited in the present study. The levels of sP-selectin, sE-selectin and sPECAM-1 did not differ significantly in cases as compared to controls (p>0.05). Hyperhomocysteinemia was significantly associated with MI in comparison with controls (p<0.001) with an odds ratio of 6.26 (95% confidence limits 3.11-12.76). Folic acid was able to correct hyperhomocysteinemia in a large majority of the cases. Although the levels of sP-selectin, sE-selectin and sPECAM-1 decreased after folic acid therapy, it was only sE-selectin which was significantly reduced (p<0.05). Thus, folic acid had a dual effect in that it reduced hyperhomocysteinemia and sE-selectin which showed a significant reduction on folate supplementation for 15 days.

Background: Circulating endothelial microparticles (EMPs), the small vesicles released from altered endothelial cells, have been established as markers of endothelial injury. The elevated count of EMPs has been described in different conditions involving endothelial injury, including acute myocardial infarction (AMI)., Aim: To assess the presence of EMP in patients with acute MI in relation to early clinical outcome and coronary angiography results., Materials and Methods: EMPs counts were determined in 66 patients pts (23 women, 43 men) with documented ST elevation AMI and in 10 control patients with no evidence of coronary artery disease. All pts with AMI underwent coronary angiography with attempted primary angioplasty. EMPs were assayed by flow cytometry in platelet-poor plasma with combinations of fluorescent antibodies (anti CD31, -51, -42) allowing distinction of EMPs from platelet microparticles. Clinical and angiography results were compared with EMP levels., Results: Three kinds of EMPs were measured: CD31+, CD51+ and CD31+/51+. The percentage of EMPs CD31+/CD51 was significantly (p=0,042) higher in patients with AMI in comparison with control subjects. However, a marker, which distinguished both groups the most, was the level of EMPs CD51+. It was significantly (p=0,024) higher in pts with AMI than in control pts. The levels of CD31+ were similar in both groups. There was no correlation between EMP levels, clinical and angiography results., Conclusion: The presence of circulating EMPs provides direct evidence of endothelial injury in AMI. The clinical and practical value of these results, however, needs further exploration.

Specific molecules including inflammatory cell adhesion molecules mediate attachment of blood leukocyte and platelets to the endothelium and mononuclear cell migration into the arterial intima. However, the clinical significance of soluble cell adhesion molecules very early in the course of acute coronary syndrome is not known. We assayed platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), intercellular adhesion molecule-1 (ICAM-1, CD54), and P-selectin (CD62P) in plasma obtained from 20 patients within 3 h after the onset of acute myocardial infarction (AMI); 16 patients with unstable angina pectoris; 20 patients with stable angina pectoris, and 28 controls. Blood samples were obtained on hospital admission and again 1 week after onset of AMI and unstable angina, and on admission in patients with stable angina and controls. Plasma PECAM-1 concentration (ng/ml) on admission was higher in patients with AMI (25.6+/-4.7) and unstable angina (24.7+/-4.4) than in stable angina (20.5+/-4.4) and control (18.8+/-3.8) groups. In both AMI and unstable angina, plasma PECAM-1 had decreased significantly by 1 week (AMI, 20.8+/-4.0; unstable angina, 21.0+/-4.1). Plasma ICAM-1 concentration (ng/ml) on admission was higher in patients with AMI (254+/-70), unstable angina (264+/-78), and stable angina (245+/-68) than in controls (201+/-56), but did not differ between the three coronary syndromes. Plasma P-selectin concentration did not differ between the four groups, including controls. Therefore, soluble PECAM-1 concentration may be a sensitive markers providing early diagnostic aid in acute coronary syndromes.

Background: Endothelial injury plays a critical role in coronary artery disease (CAD), but the assessment of this injury has been problematical. Recently, it has been shown in vitro that endothelial cells (ECs) release endothelial microparticles (EMPs) on activation or apoptosis and that an assay of EMPs can provide useful information on EC status in patients with thrombotic disorders. This study is aimed at assessing possible correlations between EMPs, which are markers of endothelial injury, and clinical subgroups of patients with CAD., Methods: A prospective, case-controlled study was conducted on 84 patients with CAD and 42 control subjects to investigate EMP profiles. Included were 64 patients with acute coronary syndromes ([ACS], 38 with myocardial infarction [MI] and 26 with unstable angina [UA]) and 20 patients with stable angina (SA). EMPs in platelet-poor plasma were measured flow cytometrically with combinations of fluorescent antibodies (anti-CD31, -51, -42), allowing distinction of EMPs from platelet microparticles (PMPs). Clinical subgroups of patients were correlated with EMP and PMP levels in blood., Results: Two species of EMPs (CD31+ and CD51+) were evaluated. Both were significantly higher in patients with CAD than in control subjects. CD31+ EMP was higher in ACS than SA. Among patients with first MI, CD31+ EMP was higher in patients with MI than in patients with UA and was significantly higher than in patients with recurring MI. CD51+ EMP did not discriminate ACS from SA. A simultaneous assay of PMP showed correlation between EMPs and PMPs. However, PMPs did not discriminate patients with SA from control subjects., Conclusions: EMP assay appears promising for assessing EC injury in CAD.

Background: Tissue damage after ischemia and reperfusion involves leukocyte endothelial interactions mediated by cell adhesion molecules. This study was designed to determine the time course of soluble adhesion molecules in patients with acute myocardial infarction after attempted reperfusion by thrombolysis with tissue plasminogen activator (tPA) or streptokinase (SK), or percutaneous transluminal coronary angioplasty (PTCA)., Methods: In 3 x 10 randomly selected patients with acute myocardial infarction undergoing thrombolysis with tPA or SK, or treated with PTCA, plasma concentrations of soluble L-selectin, P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) were measured by enzyme-linked immunosorbent assay, 30 min and 1, 2, 4, 8, 12 and 24 hours after intervention., Results: After thrombolysis with tPA, soluble L-selectin concentrations were persistently depressed and soluble PECAM-1 concentrations were elevated, compared with controls, SK and PTCA. While soluble VCAM-1 concentrations did not differ within the first hours after interventions between the three groups, soluble VCAM-1 rose by 24 hours after tPA thrombolysis but did not increase after SK and PTCA treatment. Soluble ICAM-1 concentrations were consistently elevated after PTCA compared with controls and thrombolysed patients. Soluble E-selectin was depressed after tPA thrombolysis and PTCA in comparison with controls, while the SK group showed an increase throughout the observation period. Soluble P-selectin was increased after PTCA and SK lysis up to 8 hours after treatment compared with controls, but no significant differences could be found between treatment groups., Conclusion: Adhesion molecules mediating leukocyte endothelial interactions are altered subsequent to postischemic reperfusion and by treatment with thrombolytic agents and angioplasty. The clinical relevance of these biological changes remains to be determined.

Moderate alcohol consumption (MAC) and platelet inhibition have been independently associated with a reduced risk for the development of acute myocardial infarction (AMI). The effects of MAC on the initial platelet status in patients presenting with AMI are not elucidated. Here we sought to define the effects of MAC on platelet characteristics in AMI patients before applying any reperfusion strategies. The study was designed as an analysis within the cohort study in 23 patients with AMI enrolled in the GUSTO-III. Platelets were investigated by different techniques, including aggregometry, flow cytometry, and ELISA. MAC patients exhibited mild, but consistent, inhibition of platelet aggregability, surface receptor expression, and released substances as compared to non-alcohol consuming patients. These differences were significant for 5 microM ADP (p = 0.04), 10 microM ADP-induced aggregation (p = 0.02); P-selectin (p = 0.01), and PECAM-1 (p = 0.02) platelet-bound expression. Our study confirms that moderate alcohol consumption is associated with diminished platelet activation in patients presenting with AMI. The ability of MAC to favorably modulate the pre-reperfusion platelet status in such patients is of clinical importance, and further investigation in large-scale clinical trials seem warranted.

The early identification of patients with heightened platelet activity for aggressive antiplatelet regimens represents a critical clinical issue in acute myocardial infarction (AMI) therapy. We sought to determine whether the degree of pre-reperfusion platelet function is related to subsequent activity following thrombolysis. Platelets were investigated at baseline and at 24 h following thrombolytic therapy by aggregometry, and flow cytometry in 19 AMI patients enrolled in the GUSTO-III trial. Regression analysis revealed a significant correlation for 5 microM ADP (r2 = 0.529), 10 microM ADP (r2 = 0.445), thrombin (r2 = 0.226), collagen (r2 = 0.568), and ristocetin-induced aggregation (r2 = 0.964). Platelet expression linearly correlated for GPIIb/IIIa (r2 = 0.337), P-selectin (r = 0.817), PECAM-1 (r2 = 0.586), and the vitronectin receptor (r2 = 0.634). The data suggest that the baseline characteristics predict future platelet activity, and may prospectively identify patients who will benefit most from antiplatelet strategies after coronary thrombolysis.

Animal studies have shown that the administration of antibodies against platelet/endothelial cell adhesion molecule-1 (PECAM-1) before reperfusion can reduce infarct size. The purpose of the present study was to define the effects of thrombolytic therapy in acute myocardial infarction (AMI) patients on the platelet expression and plasma concentrations of PECAM-1 at prespecified time points after attempted reperfusion. The plasma concentration and platelet expression of PECAM-1 were determined in 23 AMI patients enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial before thrombolysis and at 3, 6, 12, and 24 hours thereafter and compared with 22 healthy controls. At baseline, PECAM-1 was expressed significantly more on the platelet surface in the AMI patients than in controls (P=0.027) while soluble PECAM-1 plasma levels were almost identical between groups. There were no significant diurnal variations in both plasma and platelet PECAM-1 levels in controls. A significant decrease in platelet PECAM-1 expression was observed 3 hours after thrombolysis (P=0.03) compared with baseline, followed by a significant increase (P=0.004) in fluorescence intensity later at 24 hours after thrombolysis. Conversely, a significant increase in soluble PECAM-1 was observed 3 hours after thrombolysis (P=0.02), followed by a significant decrease later at 24 hours after attempted reperfusion (P=0.03). The expression of platelet-bound PECAM-1 is increased in AMI patients. Discordantly directed changes in soluble and platelet PECAM-1 after the first 24 hours after thrombolytic therapy may represent redistribution of the whole PECAM-1 pool. Further investigation of the possible role of PECAM-1 and the relationship between its soluble and platelet fractions in AMI are warranted.

We sought to determine plasma levels of platelet/endothelial cell adhesion molecule-1 (PECAM-1), P-selectin, and platelet-derived osteonectin, and prospectively compare these data with the discharge diagnosis in patients presenting with chest pain in a community hospital Emergency Department. Soluble antigens were measured by ELISA in 44 subjects including patients with acute myocardial infarction (AMI) (n = 13), chest pain of noncardiac origin (n = 17), and compared to those of age- and sex-matched healthy controls (n = 14). Elevated soluble PECAM-1 (64.5 +/- 18.3 ng/ml, p = 0.019), but not P-selectin (149.5 +/- 49.8 ng/ml, p = NS), nor osteonectin (549. 5 +/- 159.1 ng/ml, p = NS), occurred in the AMI group as compared to patients with noncardiac chest pain (46.2 +/- 7.5 ng/ml, 118.2 +/- 40.1 ng/ml, and 619.4 +/- 74.4 ng/ml, respectively). Increased plasma PECAM-1 may serve as a useful marker in the early detection of patients with AMI. Larger studies will be necessary to confirm the utility of soluble PECAM-1 in identifying AMI among patients presenting with chest pain.

Aspirin therapy and platelet inhibition reduce the risk for the development of acute myocardial infarction (AMI). However, the effects of aspirin on baseline platelet activity in patients presenting with AMI are not known. We determined the effect of long-term aspirin use on baseline platelet activity in patients presenting with AMI, enrolled in the GUSTO-III Platelet Study. Platelet characteristics were investigated by aggregometry, flow cytometry and enzyme-linked immunosorbent assay in 23 patients before thrombolysis. Sixteen AMI patients were aspirin free, and 7 patients were using aspirin (81-500 mg/daily). The aspirin-treated patients exhibited a mild but consistent reduction of platelet activity which reached significance for 5 microM (p = 0.02), and 10 microM (p = 0.01) adenosine diphosphate induced aggregation. The surface expression of P-selectin (p = 0.02) and PECAM-1 (p = 0.03) and the plasma level of soluble P-selectin (p = 0.02) were also reduced. As previously observed in normal humans and patients with stable coronary artery disease, long-term aspirin therapy is also associated with diminished platelet activation in patients presenting with AMI. Long-term aspirin therapy mildly reduces baseline platelet activity; however, this degree of relative platelet inhibition does not appear to be cardioprotective.

Background: Platelets play a pivotal role in the pathogenesis of acute myocardial infarction and their activation can cause thrombolysis to fail., Methods: Baseline aggregation of platelets and expression of major surface receptors measured by flow cytometry were compared with clinical outcome after thrombolysis for 23 patients enrolled in the GUSTO-III trial., Results: Failure to reperfuse (n = 3) and recurrent ischemia (n = 2) were observed in five patients who subsequently underwent emergency angioplasty. These patients were treated later in their course of disease than were the 18 patients who were successfully reperfused and remained free of recurrent ischemia. Greater than normal expression of platelet P-selectin (33.7 +/- 1.1 versus 28.1 +/- 1.9, P = 0.01) and expression of platelet--endothelial cell adhesion molecule-1 (PECAM-1; (57.1 +/- 2.3 versus 50.2 +/- 2.8, P = 0.02) were observed in members of the group with recurrent ischemia or failed reperfusion., Conclusion: Greater than normal baseline expression of P-selectin and PECAM-1 platelet receptors was correlated to delayed and unsuccessful coronary thrombolysis among patients presenting with acute myocardial infarction.

Background: Antibodies to selected neutrophil or endothelial cell adhesion molecules decrease myocardial infarct size in vivo. Platelet/endothelial cell adhesion molecule-1 (PECAM-1) is an immunoglobulin gene superfamily member expressed constitutively on neutrophils and endothelium. F(ab')2 fragments of antibody against PECAM-1 inhibit transendothelial migration of neutrophils in several in vivo models of acute inflammation. Therefore, we examined the effect of F(ab')2 fragments of anti-PECAM-1 antibody in a rat model of myocardial infarction., Methods and Results: F(ab')2 fragments of the anti-PECAM-1 antibody SEW16 and control normal rabbit IgG (NRIgG) were administered at 5 mg/kg to male Wistar rats, and the rats were subjected to a 30-minute coronary artery occlusion followed by 2 hours of reperfusion. At the completion of each experiment, the area at risk, infarct size (IS), and myeloperoxidase (MPO) activity were determined. Compared with untreated (n = 8; IS, 57 +/- 5%) or NRIgG-treated (n = 10; IS, 62 +/- 3%) control rats, SEW16-treated rats (n = 15; IS, 28.5 +/- 4%) displayed a 54% decrease in myocardial infarct size (P < .001). Hemodynamic parameters, leukocyte counts, total left ventricular weight, and area-at-risk weights did not differ significantly between the treatment groups. However, measurement of MPO activity revealed that neutrophil accumulation was reduced 83% (NRIgG, 975 +/- 55 mU/g; SEW16, 167 +/- 62 mU/g)., Conclusions: These results demonstrate that blocking PECAM-1 exerts a significant protective effect in a rat model of myocardial ischemia-reperfusion injury via blockade of neutrophil accumulation in the myocardium.