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1.
Sci Rep ; 10(1): 3175, 2020 02 21.
Article in English | MEDLINE | ID: mdl-32081968

ABSTRACT

Antiplatelet drugs are prescribed without considering the diabetic status of the patient. The objective of the current investigation was to determine the impact of clinical factors, CYP4F2 enzyme and 20-hydroxyeicosatetraenoic acid (20-HETE) concentrations on high on-treatment platelet reactivity in patients with diabetes treated with antiplatelet drugs following acute coronary syndromes. A total of 667 patients were included in the study. Dual antiplatelet drug loading dosages with aspirin (300 mg) and ticagrelor (180 mg) or clopidogrel (600 mg) were prescribed to all the studied patients. Testing of platelet aggregation was performed the day after loading antiplatelet drug dosages. Platelet aggregation test was done according to the classical Born method. Multivariate binary regression analysis demonstrated that insulin use and higher 20-HETE concentration increased the odds of high on-treatment platelet reactivity during the initiation of antiplatelet drug therapy (OR: 3.968, 95% CI: 1.478-10.656, p = 0.006 and OR: 1.139, 95% CI: 1.073-1.210, respectively, p < 0.001). Ticagrelor use decreased the odds of developing high on-treatment platelet reactivity (OR: 0.238, 95% CI: 0.097-0.585, p = 0.002). Data from this study revealed that high on-treatment platelet reactivity during dual antiplatelet therapy in patients with diabetes may depend on such factors as insulin prescription and 20-HETE concentration.


Subject(s)
Acute Coronary Syndrome/drug therapy , Blood Platelets/pathology , Diabetes Mellitus/pathology , Platelet Aggregation Inhibitors/therapeutic use , Acute Coronary Syndrome/blood , Adult , Aged , Aged, 80 and over , Blood Platelets/drug effects , Cytochrome P450 Family 4/blood , Diabetes Mellitus/blood , Female , Humans , Hydroxyeicosatetraenoic Acids/blood , Logistic Models , Male , Middle Aged , Multivariate Analysis , Platelet Aggregation Inhibitors/pharmacology
2.
Biomarkers ; 25(1): 40-47, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31694408

ABSTRACT

Purpose: To find an association of relative expression of hsa-miR-24-3p and hsa-miR-34a-5p molecules and CYP4F2 enzyme activity in blood plasma of stable angina pectoris (AP) patients'.Materials and Methods: MiRNA gene expression analysis was performed on total RNA extracted from blood plasma, using quantitative real-time polymerase chain reaction. CYP4F2 enzyme levels were determined using commercial ELISA kit. In total, 32 AP and 15 control samples were examined.Results: The relative expression of hsa-miR-24-3p and hsa-miR-34a-5p was upregulated by 4.4 (p = 0.0001) and 3.8 (p = 0.005) -fold in AP patient's blood plasma compared to control subjects. CYP4F2 enzyme level in blood plasma were 2.1 (p = 0.001) times lower in AP patients. Circulating hsa-miR-24-3p was negatively associated with CYP4F2 enzyme level (Spearman correlation coefficient rank r= -0.32; p = 0.03). Moreover, patients that were taking atorvastatin, had 1.5 (p = 0.04) times higher hsa-miR-24-3p expression in blood plasma.Conclusions. Our data suggest that hsa-miR-24-3p might have an effect on CYP4F2 activity during atherosclerosis.


Subject(s)
Angina, Stable/blood , Circulating MicroRNA/blood , Cytochrome P450 Family 4/blood , MicroRNAs/blood , Adult , Aged , Aged, 80 and over , Angina, Stable/drug therapy , Angina, Stable/enzymology , Angina, Stable/genetics , Biomarkers/blood , Case-Control Studies , Circulating MicroRNA/genetics , Female , Humans , Male , MicroRNAs/genetics , Middle Aged , Pilot Projects , Up-Regulation
3.
Rheumatology (Oxford) ; 58(2): 345-351, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30247644

ABSTRACT

Objective: Monosodium urate-induced inflammation plays a vital role in acute gout (AG). Inflammation is a multi-stage process involved in the acute release of arachidonic acid and its metabolites. However, the function of the metabolism of arachidonic acid and other polyunsaturated fatty acids in AG is not well understood. This study aimed to investigate the modification of polyunsaturated fatty acid metabolism by AG. Methods: Plasma samples from patients with an AG attack (n = 26) and gender-matched healthy controls (n = 26) were analysed by metabolic profiling of polyunsaturated fatty acids. The findings were further validated with a second cohort (n = 20 each group). The associated mechanisms were investigated in whole blood cells from the second cohort and neutrophils in vitro. Results: Plasma metabolic profiling revealed a significant increase in leukotriene B4 (LTB4) for AG patients in both cohorts. The increase in plasma LTB4 was accounted for by the dynamic balance between the activation of 5-lipoxygenase and CYP4F3, the former mediating the biosynthesis of LTB4 and the latter mediating its metabolism. This was supported by significantly increased transcriptional levels of 5-lipoxygenase and CYP4F3 in whole blood cells from AG patients compared with those of controls, and the uric acid-caused dose-relevant and time-dependent activation of 5-lipoxygenase and CYP4F3 at the transcriptional and molecular levels in vitro. Conclusion: Increased LTB4 in AG patients is mainly due to activation of 5-lipoxygenase. 5-Lipoxygenase inhibition may be of therapeutic value clinically.


Subject(s)
Arachidonate 5-Lipoxygenase/blood , Arthritis, Gouty/enzymology , Acute Disease , Adolescent , Adult , Aged , Arthritis, Gouty/blood , Case-Control Studies , Cells, Cultured , Cytochrome P450 Family 4/blood , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Enzyme Activation/physiology , Fatty Acids, Unsaturated/blood , Female , Humans , Leukotriene B4/blood , Male , Metabolome/physiology , Middle Aged , Neutrophils/drug effects , Neutrophils/metabolism , Uric Acid/administration & dosage , Uric Acid/pharmacology , Young Adult
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