Impact of clopidogrel and aspirin treatment on the expression of proteins in platelets from type-2 diabetic patients with stable coronary ischemia
Cardiovascular Research Unit, Cardiovascular Institute, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid 28040, Spain. Journal of Pharmaceutical Sciences
(Impact Factor: 2.59).
08/2012; 101(8):2821-32. DOI: 10.1002/jps.23201
The purpose of this study was to compare the effect of dual antiplatelet therapy [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia. Patients had been taking ASA (100 mg day) and they were randomized to receive (n = 29) or not (n = 28) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form. Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry. The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy chain was changed after dual antiplatelet therapy. Plasma level of platelet factor 4 (PF4), an in vivo marker of platelet activity, was not different between both groups. These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients. However, the variation in platelet proteome was lower than it would be initially expected, taking into account the apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma level was not further decreased in the platelets treated for a longer time than 9-12 months with ASA + clopidogrel, as compared with ASA alone.
Figures in this publication
Available from: Jinesh Nagavi
[Show abstract] [Hide abstract]
ABSTRACT: Objectives: Objective of our present study was to develop a novel ultra fast liquid chromatographic method for quantitative simultaneous
estimation of Clopidogrel, Pantoprazole & Rosuvastatin in human plasma and to validate the developed method following USFDA guidelines.
Methods: In the current study, the analysis was performed on phenomenex C8 (250 × 4.6 mm, 5μm) column using phosphate buffer (pH-2.5) and
acetonitrile (45: 55 v/v) as mobile phase at flow rate of 1.2 mL/min. The system consisted of a pump (Shimadzu, prominence, UFLC), with 20 µl
sample injector, along with a PDA detector at a wavelength of 254, 243 nm and 220 nm
Results: In this developed method Clopidogrel, Pantoprazole & Rosuvastatin, eluted at a retention time of 2.566, 5.002 and 9.301 min respectively.
The proposed method is having linearity in the concentration range from 5 to 50μg/mL of Clopidogrel, Pantoprazole & Rosuvastatin. The current
method was validated with respect to accuracy, linearity; precision, lowest limit of quantification (LLOQ) and recovery according to the USFDA
guidelines. A good linear relationship over the concentration range of 5-50µg/ml was shown. Validation of the method was carried out as per the
USFDA draft guidelines.
for Clopidogrel, Pantoprazole and Rosuvastatin respectively.
Data was compiled using Shimadzu LC Solution software.
Conclusion: A novel specific, accurate, precise UFLC method was developed for quantitative simultaneous estimation of Clopidogrel, Pantoprazole
& Rosuvastatin in human plasma and validated. The developed method is suitable and economic for routine analysis and pharmacokinetic studies of
Clopidogrel, Pantoprazole & Rosuvastatin simultaneously. The method developed was found to be precise, accurate, specific, linear and sensitive.
Statistical analysis shows that the method is reproducible and selective for the estimation of Clopidogrel, Pantoprazole & Rosuvastatin in dosage form of patient plasma.
Keywords: Bioanalytical, Clopidogrel, Pantoprazole & Rosuvastatin, RP-UFLC, USFDA.
International Journal of Pharmacy and Pharmaceutical Sciences 01/2014; 6(9):490-496. · 1.59 Impact Factor
Available from: Paula Vélez
[Show abstract] [Hide abstract]
ABSTRACT: In recent years, platelet proteomics has been applied successfully to the study of cardiovascular diseases (CVDs). It is very well known that platelets play a pivotal role in the pathophysiological mechanisms underlying many CVDs, especially acute coronary syndromes (ACSs), since they are implied in thrombus formation after atheroma plaque rupture. This is the reason why molecules involved in platelet activation and aggregation are primary targets for treatment of ACSs. Many efforts are aimed at finding drugs that inhibit platelet activation; however it is difficult to separate the therapeutic benefits from harmful effects because pathological and physiological functions of platelets are due to the same mechanisms. Given that platelets lack a nucleus, proteomics is regarded as an ideal method to approach their biochemistry. Current platelet proteomic studies are focusing on the identification of platelet molecular and functional changes in normal and pathological states, enriching the comprehension of platelet biological function, and screening for new biomarkers and antiplatelet agents. In the present article, we introduce the reader to platelet biology and function, and revise recent advances in platelet proteomics applied to the study of CVDs, including a special emphasis on sample preparation requirements for proteome analysis of platelet clinical samples.
Translational Proteomics 10/2014; 7. DOI:10.1016/j.trprot.2014.09.002
Available from: onlinelibrary.wiley.com
[Show abstract] [Hide abstract]
ABSTRACT: Antiplatelet agents represent the mainstay of acute coronary syndrome (ACS) therapy to prevent ischemic events and to improve safety in patients undergoing percutaneous coronary intervention. However, despite the availability of several drugs and the use of dual antiplatelet therapy, the pharmacological response is highly variable with a subset of patients continuing to experience recurrent thrombotic events, revealing a wide variability in platelet response to antiplatelet drugs. Several factors may explain this, including genetic variation and environmental factors. Here we look at the application of proteomic analysis, an approach that provides an integrated readout of these diverse influences.
© 2015 International Society on Thrombosis and Haemostasis.
Journal of Thrombosis and Haemostasis 06/2015; 13 Suppl 1(S1):S323-S331. DOI:10.1111/jth.12943 · 5.72 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.