Resistance to Acetylsalicylic Acid in Patients with Coronary Heart Disease Is the Result of Metabolic Activity of Platelets

Grinshtein, Yu. I.; Савченко, А. А.; Косинова, А. А.; Goncharov, Maxim

doi:10.3390/ph13080178

Cited by 5 publications

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References 56 publications

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“…Примечательно, что в группе рАСК пациентов с ИБС (монотерапия АСК) уровень и интенсив- [11]. То есть чувствительность связана с повышенной метаболической актив ностью тромбоцитов по синтезу АФК, в т.ч.…”

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Molecular and metabolic characteristics of changes in the platelet sensitivity to antiplatelet therapy in patients with coronary artery disease before and after coronary artery bypass grafting

et al. 2021

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Aim. To study the production of reactive oxygen species (ROS) by platelets in patients with coronary artery disease (CAD) before and after coronary artery bypass grafting (CABG), depending on their sensitivity to acetylsalicylic acid (ASA) as a part of ASA monotherapy and dual antiplatelet therapy (DAPT) (ASA+clopidogrel).Material and methods. The study included 104 patients with CAD (ASA monotherapy, 64 patients; DAPT, 40 patients). From day 1 after CABG, they took 100 mg a day of enteric-coated ASA. In the DAPT group, clopidogrel was prescribed for 2-3 days after CABG. All measurements were performed before surgery, on the 1st day and days 8-10 after surgery. Control group consisted of 36 healthy donors. Resistance to ASA was determined at a level of optical platelet aggregation with arachidonic acid >20% at least at one observation point. The spontaneous and ADP-induced chemiluminescence (CL) of platelets with luminol and lucigenin was assessed according to the following parameters: time to maximum intensity (Tmax), maximum intensity (Imax), area (S) under the CL curve, and the ratio of ADP-induced CL S to spontaneous CL S.Results. Throughout the study, 71 patients with CAD were sensitive to ASA (sASA) (ASA monotherapy, 46 patients; DAPT, 25 patients), three patients — resistant (rASA) (ASA monotherapy, 1; DAPT, 2). Sensitivity of other 30 patients (ASA monotherapy, 17; DAPT, 13) changed in different follow-up periods. Compared to the control group, sASA patients had increased values of platelet CL parameters throughout the study, while in the rASA group (ASA monotherapy), Tmax was higher before CABG, and in the rASA group (ASA therapy+clopidogrel), Imax and S were higher on the first day after CABG, while Imax — on days 8-10 after CABG. Compared to sASA, the values of S and Imax before CABG, Imax after CABG, as well as Imax and S on the days 8-10 after CABG in rASA (ASA monotherapy) were significantly lower, while in rASA (ASA therapy+clopidogrel), only the Tmax values were lower on the 8-10 days after CABG.Conclusion. In patients with CAD, depending on the sensitivity to ASA and antiplatelet therapy after CABG, the metabolic activity of platelets in terms of ROS production differs. In sASA patients, ROS synthesis is higher than in healthy individuals, while, in rASA patients (ASA monotherapy), platelets produce ROS levels lower than in sASA. CABG surgery and the addition of clopidogrel to ASA therapy leads to increased ROS production in rASA patients in the postoperative period.

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Molecular and metabolic characteristics of changes in the platelet sensitivity to antiplatelet therapy in patients with coronary artery disease before and after coronary artery bypass grafting

et al. 2021

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DFT investigation of nonlinear optical response of organic compound: acetylsalicylic acid

Rana

Yadav

Chowdhury

2023

International Journal of Materials Research

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Nonlinear optical studies of organic compounds have been widely conducted because of its great scope in molecular engineering. In the present work, we have chosen an organic compound acetylsalicylic acid due to its non-centrosymmetric structure and presence of extended conjugated π-system. Nonlinear optical response of the probe system has been explored computationally by using density functional theory with B3LYP/6-311G++(d,p) basis set. To explore the nonlinear optical response, Mulliken charge analysis, Raman, UV–vis, nuclear magnetic resonance, molecular electrostatic potential analysis, polarizability, first order hyperpolarizability etc., have been applied for the probe molecule. Observed high value of dipole moment of optimized structure, charge transfer in the system, high Raman activity, and high value of polarizability, first order hyperpolarizability validate the strong candidature of acetylsalicylic acid to be used as a nonlinear optical active material in the future.

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Postgenomic aspects of resistance to acetylsalicylic acid in patients with coronary artery disease

Grinshtein,

Kosinova,

Maltseva

et al. 2024

Russ J Cardiol

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Aim. To study the expression level of the P-selectin gene (SELP) mRNA and the level of intercellular interaction in patients with coronary artery disease (CAD) before and after coronary artery bypass grafting (CABG) in patients with resistance to acetylsalicylic acid (ASA).Material and methods. The study included 65 patients with CAD who were scheduled to CABG. SELP expression, the platelet-leucocyte aggregate level, and the level of P-selectin expression on aggregates were determined in all participants. Resistance to ASA was defined as platelet aggregation with arachidonic acid ≥20% in at least one sample. All studies were performed before and on the 8th-10th day after CABG.Results. Among patients, 29,4% (n=30) were resistant to ASA (ASA-R) at least at one point, while 7,8% (n=8) acquired resistance after CABG. ASA-R had a higher level of SELP (0,41 [0,28; 0,48] vs 0,32 [0,23; 0,39], p=0,037), absolute content of monocyte-platelet aggregates (24,70 [9,69; 39,90] vs 10,15 [5,27; 30,63], p=0,037) and relative amount of platelet-platelet CD62P aggregates (7,37% [3,43; 35,49] vs 4,84% [0,90; 9,63], p=0,045). A negative correlation was found between SELP expression and the relative content of monocyte-platelet aggregates (ρ=-0,349, p=0,013) on days 8-10 after CABG. Mmultivariate regression analysis found that the level of SELP gene mRNA expression is a predictor of ASA resistance before CABG (odds ratio 404,48; 95% confidence interval 1,68-97461,63).Conclusion. Increased SELP expression is associated with an increase in platelet aggregation activity, which contributes to an insufficient platelet response to antithrombotic therapy in patients with CABG. The level of SELP gene mRNA expression can be considered as a predictor of ASA resistance.

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Resistance to Acetylsalicylic Acid in Patients with Coronary Heart Disease Is the Result of Metabolic Activity of Platelets

Cited by 5 publications

References 56 publications

Molecular and metabolic characteristics of changes in the platelet sensitivity to antiplatelet therapy in patients with coronary artery disease before and after coronary artery bypass grafting

Molecular and metabolic characteristics of changes in the platelet sensitivity to antiplatelet therapy in patients with coronary artery disease before and after coronary artery bypass grafting

DFT investigation of nonlinear optical response of organic compound: acetylsalicylic acid

Postgenomic aspects of resistance to acetylsalicylic acid in patients with coronary artery disease

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