Reduced inhibition by abciximab in platelets with the PlA2 polymorphism

Wheeler, Guy L.; Braden, Gregory A.; Bray, Paul F.; Marciniak, Stanley J.; Mascelli, Mary Ann; Sane, David C.

doi:10.1067/mhj.2002.119763

Cited by 69 publications

(43 citation statements)

References 31 publications

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“…1,30 In patients undergoing percutaneous coronary intervention, heterozygous Leu33/Pro33 platelets were inhibited by abciximab to a lesser extent than Leu33/Leu33 platelets in an in vitro platelet function assay. 31 This effect may be different in young healthy subjects. 7 However, no information is available to indicate whether these commonly used therapies are modulated by the Leu33Pro polymorphism for outcomes after PCTA.…”

Section: Discussionmentioning

confidence: 99%

Pl^APolymorphism of Integrin β₃Differentially Modulates Cellular Migration on Extracellular Matrix Proteins

Sajid

Vijayan

Souza

et al. 2002

ATVB

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Objective-Cell migration is central to multiple physiological and pathologic processes and involves interactions between integrins on the cell surface and the extracellular matrix. The Leu33Pro (Pl A ) polymorphism of integrin ␤ 3 has been reported to be associated with a greater rate of restenosis after angioplasty, a process involving endothelial and smooth muscle cell migration. We have addressed the possibility that the Leu33Pro polymorphism could modify the migratory behavior of Chinese hamster ovary (CHO) cells expressing the ␤ 3 -containing integrin complexes. Methods and Results-Haptotactic migratory responses of CHO ␣ IIb ␤ 3 cells to fibronectin and vitronectin were not statistically different between the Leu33 and Pro33 cells. However, CHO cells with the Pro33 (Pl A2 ) polymorphism had an enhanced haptotactic migratory response to fibrinogen and von Willebrand Factor. This enhanced migration (1) could be blocked by the ␣ IIb ␤ 3 -complex-specific neutralizing mAb 10E5, by 7E3, a neutralizing mAb specific for the ␤ 3 integrin, and by the ␣ IIb ␤ 3 -blocking peptide Integrilin; (2) was not observed with a CHO cell line expressing an activating ␤ 3 Cys435 to Ala mutation; and (3) was attributable to increased activity of mitogen-activated protein kinase and cyclooxygenase. CHO cell lines expressing the Pro33 isoform of ␣ v ␤ 3 had an enhanced haptotactic migratory response to vitronectin and osteopontin but not fibrinogen. Conclusions-The

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Section: Discussionmentioning

confidence: 99%

Pl^APolymorphism of Integrin β₃Differentially Modulates Cellular Migration on Extracellular Matrix Proteins

Sajid

Vijayan

Souza

et al. 2002

ATVB

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“…Genotyping for integrin b 3 Leu33Pro might be useful not only before ovarian cancer diagnosis, but also for prognostic purposes, perhaps in combination with measurement of its ligand osteopontin (Brakora et al 2004, Coppola et al 2004, Schorge et al 2004. Finally, in the future, genotyping at the time of diagnosis might also assist in drug selection: blockade of integrin b 3 -mediated signal transduction inhibits growth of human ovarian cancer cell lines (Szaniawska et al 2001, Cruet-Hennequart et al 2003, and interaction between integrin b 3 and its agonists and antagonists depends on Leu33Pro genotype (Michelson et al 2000, Boncler et al 2002, Wheeler et al 2002, Angiolillo et al 2004). …”

Section: Discussionmentioning

confidence: 99%

Increased risk of ovarian cancer in integrin β3 Leu33Pro homozygotes

Bojesen¹,

Kjær²,

Høgdall³

et al. 2005

Endocr Relat Cancer

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We previously demonstrated that integrin b 3 Leu33Pro homozygotes have an increased risk of cancer, possibly most pronounced for ovarian cancer. We now test the latter hypothesis in casecontrol and prospective studies. We genotyped 463 Danish women with ovarian cancer, and 4291 women from the Danish general population. Calculation of odds ratios by conditional logistic regression was performed in the case-control study (n=463+3543), and of ovarian cancer incidence, log-rank statistics and hazard ratios by Cox regression in the prospective study (n=4291) with 9.5-year follow-up. In the case-control study matched for age and marital status, the odds ratio for ovarian cancer in homozygotes versus non-carriers was 1.6 (95% confidence interval: 1.0-2.6). In the prospective study with 28 incident ovarian cancers, non-carriers and homozygotes had incidences of 7 (4-11) and 30 (10-92) per 10 000 person-years (log-rank P=0.02). The ageadjusted hazard ratio for ovarian cancer in homozygotes versus non-carriers was 3.9 (1.1-13). Risk of ovarian cancer did not differ between heterozygotes and non-carriers in either study. Integrin b 3 Leu33Pro homozygotes have an increased risk of ovarian cancer.

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“…25 Wheeler et al showed that there was less platelet inhibition through using abciximab in patients with the PlA2 mutation who underwent percutaneous coronary intervention. 26 Weber et al…”

Section: After Tirofiban Administrationmentioning

confidence: 99%

“…[25][26][27][28] However, variability of platelet response to GPIIbIIIa inhibitors exists and can be correlated with other factors, such as drug dose-dependence, the method used to assess platelet aggregation, pharmacodynamics, concomitant use of dual antiplatelet aggregation, rheological characteristics of blood coagulation and other such things. Khaspekova et al analyzed the platelet response among patients with acute coronary syndrome and found that the expression of platelet GPIb and GPIIbIIIa correlated with the average volume of platelets and not the genetic polymorphism of the GPIIIa Leu33Pro and GPIbα Thr145Met mutations.…”

Section: After Tirofiban Administrationmentioning

confidence: 99%

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

et al. 2016

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CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. DESIGN AND SETTING: Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. METHOD: Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T), Ib (Thr/Met), IIb (Ile/Ser) and IIIa (PIA) were the mutations selected. RESULTS: Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. CONCLUSIONS: Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction. RESUMO CONTEXTO E OBJETIVOS:Inibidores da glicoproteína (abciximab, eptifibatide, tirofiban) são utilizados em pacientes com angina instável e infarto do miocárdio sem elevação do segmento ST (IAMSSST) antes da intervenção coronária percutânea. Dentre eles, o tirofiban é o menos eficaz. Nossa hipótese é que a resposta ao tirofiban possa estar associada a mutações no gene da glicoproteína. DESENHO E LOCAL: Estudo prospectivo na Unidade de Emergência do Instituto do Coração (InCor), Universidade de São Paulo (USP).MÉTODOS: Foram analisadas a evolução intra-hospitalar e agregabilidade plaquetária em resposta ao tirofiban de 4 mutações da glicoproteína em 50 pacientes com indicação para intervenção coronária percutânea, 17 (34%) com angina instável e 33 (66%) com IAMSSST. A agregação plaquetária foi analisada pelo método de Born. Amostras de sangue foram obtidas antes e uma hora após infusão do tirofiban. As glicoproteínas Ia (807C/T), Ib (Thr/Met), IIb (Ile/Ser) e IIIa (PIA) foram as mutações selecionadas. RESULTADOS: Hipertensão, dislipidemia, diabetes, tabagismo, doença coronariana e acidente vascular cerebral prévios foram semelhantes entre os grupos. Observou-se menor agregabilidade plaquetária dos genótipos mutantes da...

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Reduced inhibition by abciximab in platelets with the PlA2 polymorphism

Cited by 69 publications

References 31 publications

Pl^APolymorphism of Integrin β₃Differentially Modulates Cellular Migration on Extracellular Matrix Proteins

Pl^APolymorphism of Integrin β₃Differentially Modulates Cellular Migration on Extracellular Matrix Proteins

Increased risk of ovarian cancer in integrin β3 Leu33Pro homozygotes

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

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Reduced inhibition by abciximab in platelets with the PlA2 polymorphism

Cited by 69 publications

References 31 publications

PlAPolymorphism of Integrin β3Differentially Modulates Cellular Migration on Extracellular Matrix Proteins

PlAPolymorphism of Integrin β3Differentially Modulates Cellular Migration on Extracellular Matrix Proteins

Increased risk of ovarian cancer in integrin β3 Leu33Pro homozygotes

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

Contact Info

Product

Resources

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Pl^APolymorphism of Integrin β₃Differentially Modulates Cellular Migration on Extracellular Matrix Proteins

Pl^APolymorphism of Integrin β₃Differentially Modulates Cellular Migration on Extracellular Matrix Proteins