Platelets in atherothrombosis

Ruggeri, Zaverio M.

doi:10.1038/nm1102-1227

Cited by 1,417 publications

(1,224 citation statements)

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“…First, during the acute phase of AMI, more platelets are released and overactivated 1, 19. Newly formed platelets beside their constitutive cyclooxygenase (COX)‐1 expression, retain COX‐2 activity contributing to additional TX synthesis 1, 2, 11, 20, 21.…”

Section: Discussionmentioning

confidence: 99%

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Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Szczeklik

Stodółkiewicz

Rzeszutko

et al. 2016

JAHA

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BackgroundUrinary 11‐dehydro‐thromboxane (TX)B2 has been described as a potential predictive biomarker of major adverse cardiovascular events (MACEs) in high cardiac risk patients. This part of LTIMI (Leukotrienes and Thromboxane In Myocardial Infarction) study aimed to evaluate the relationship between 11‐dehydro‐TXB 2 and MACEs in patients with acute myocardial infarction (AMI).Methods and Results LTIMI was an observational, prospective study in 180 consecutive patients with AMI type 1 referred for primary percutaneous coronary intervention. On admission and at follow‐up visits (1 month, 1 year), 11‐dehydro‐TXB 2 was measured in urinary samples by using high‐performance liquid chromatography–tandem mass spectrometry. The primary outcome was occurrence of composite MACEs during 1‐year after AMI. Left ventricular ejection fraction was assessed in echocardiography on admission and at 1‐year follow‐up. Analyses of 11‐dehydro‐TXB 2 (pg/mg creatinine) were performed on log‐transformed data and expressed as median with IQR (Q1–Q3). 11‐Dehydro‐TXB 2 level on admission was 7.39 (6.85–8.01) and decreased at 1 month (6.73, 6.27–7.12; P<0.001) and 1‐year follow‐up (6.37, 5.91–6.94; P<0.001). In univariate analysis, baseline 11‐dehydro‐TXB 2 was higher in patients with MACEs (n=60; 7.73, 7.07–8.60) compared with those without MACEs (n=119; 7.28, 6.68–7.79; P=0.002). In multivariate regression model, 11‐dehydro‐TXB 2 and 3 other variables (diabetes, multivessel disease, and left ventricular ejection fraction) were found to be best 1‐year cumulative MACE predictors with odds ratio for 11‐dehydro‐TXB 2 of 1.58 (95% CI 1.095–2.33; P=0.017) and area under the curve (in receiver operating characteristic analysis of 0.8). Baseline 11‐dehydro‐TXB 2 negatively correlated with both left ventricular ejection fraction on admission (R=−0.21; P=0.006) and after 1 year (R=−0.346; P<0.001).Conclusions11‐Dehydro‐TXB 2 predicts 1‐year cumulative MACEs in AMI patients and provides prognostic information on the left ventricular performance.

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Section: Discussionmentioning

confidence: 99%

“…Thromboxane (TX)A 2 is a potent platelet agonist and vasoconstrictor1 produced mostly by platelets, which play a pivotal role in thrombogenesis at sites of vulnerable plaque and provide a strong rationale for blocking their function in the setting of acute myocardial infarction (AMI) 1, 2…”

Section: Introductionmentioning

confidence: 99%

Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Szczeklik

Stodółkiewicz

Rzeszutko

et al. 2016

JAHA

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“…Several reasons lead us to exploit the distribution of GPIba alleles among Brazilians, such as the central role of platelet adhesion in the atherosclerosis process and the unique characteristic of the GPIba gene, which is encoded by a single exon [1,4,39]. All three characterized polymorphisms are located either in the promoter or in the coding region, which influence the amount of the receptor expression and/or its function [5,6,15,16].…”

Section: Discussionmentioning

confidence: 99%

“…Disruption of the murine GPIba gene recapitulates closely the human disease [3]. Platelets also participate in atherogenesis and subsequent formation of occlusive thrombi is dependent on platelet adhesion to the atherosclerotic plaque rupture [4].…”

Section: Introductionmentioning

confidence: 95%

Genetic variability of platelet glycoprotein Ibα gene

et al. 2004

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Platelet membrane glycoprotein (GP) Ibα is a critical component of platelet adhesion complex to subendothelium structures following tissue injury or pathological surfaces, such as atherosclerotic plaques. Polymorphisms of the GPIbα gene have been associated with a high risk for occlusive vascular disease, and its distribution varies considerably among distinct populations. These polymorphisms comprise the human platelet antigen (HPA)‐2 system, the −5C/T dimorphism of the Kozak sequence, and the variable number of tandem 39‐bp repeats (VNTR). Here we report the prevalence of the GPIbα gene polymorphisms among Brazilians, a highly ethnically diverse population. We analyzed 492 subjects of European, African, or Indigenous origin. It was possible to determine ten distinct haplotypes. The most common (∽40%) haplotype was the Kozak‐TT/HPA‐2aa/VNTR‐CC for both Caucasian and African descent. However, among Indigenous, Kozak‐TT/HPA‐2aa/VNTR‐CC and Kozak‐TC/HPA‐2aa/VNTR‐CC were equally present. Although a strong linkage disequilibrium between VNTR and HPA‐2 polymorphism had also been observed, here we determined incomplete linkage disequilibrium in 10% of subjects from all ethnic groups. VNTR‐E, a rare variant lacking the 39‐bp repeat, was identified in two unrelated subjects, and functional platelet studies revealed no abnormalities. The VNTR‐A allele, the largest variant containing four copies of the repeats, was not identified in this population. However, homozygosity for the VNTR‐A allele (Kozak‐TT/HPA‐2aa/VNTR‐AA) was determined in two distinct species of nonhuman primates. These results suggest a greater complex evolutionary mechanism in the macroglycoprotein region of the GPIbα gene and may be useful in the design of gene–disease association studies for vascular disease. Am. J. Hematol. 77:107–116, 2004. © 2004 Wiley‐Liss, Inc.

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“…As thrombi occluding coronary arteries were platelet rich in content, platelet activation and aggregation are considered to be central to pathogenic thrombus production [5,6]. Antiplatelet agents have been extensively researched and developed as potential therapies for both the treatment and prevention of cardiovascular disease [7,8].…”

Section: Introductionmentioning

confidence: 99%

Antiplatelet activity of BRX-018, (6aS,cis)-Malonic acid 3-acetoxy-6a9-bis-(2-methoxycarbonyl-acetoxy)-6,6a,7,11b-tetrahydro-indeno[2,1-c]chromen-10-yl ester methylester

Lee

Chang

Lee

et al. 2005

Thrombosis Research

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Platelets in atherothrombosis

Cited by 1,417 publications

References 73 publications

Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Genetic variability of platelet glycoprotein Ibα gene

Antiplatelet activity of BRX-018, (6aS,cis)-Malonic acid 3-acetoxy-6a9-bis-(2-methoxycarbonyl-acetoxy)-6,6a,7,11b-tetrahydro-indeno[2,1-c]chromen-10-yl ester methylester

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Platelets in atherothrombosis

Cited by 1,417 publications

References 73 publications

Urinary 11‐Dehydro‐Thromboxane B 2 as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Urinary 11‐Dehydro‐Thromboxane B 2 as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Genetic variability of platelet glycoprotein Ibα gene

Antiplatelet activity of BRX-018, (6aS,cis)-Malonic acid 3-acetoxy-6a9-bis-(2-methoxycarbonyl-acetoxy)-6,6a,7,11b-tetrahydro-indeno[2,1-c]chromen-10-yl ester methylester

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Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study