A novel mechanism of ACE inhibition–associated enhanced platelet reactivity: disproof of the ARB-MI paradox?
| Autor: | Malte Kelm, Tobias Petzold, Thomas Hohlfeld, Aysel Ayhan, René M'Pembele, Maria Grandoch, Carolin Helten, Tobias Zeus, Bodo Levkau, Amin Polzin, Verena Veulemans, Philipp Mourikis, Lisa Dannenberg, Kajetan Trojovsky, Christina Kohlmorgen |
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| Rok vydání: | 2020 |
| Předmět: |
Blood Platelets
Male Time Factors Platelet Aggregation Platelet Function Tests Medizin Angiotensin-Converting Enzyme Inhibitors Pilot Projects Angiotensin II Receptor Blockers Pharmacology 030226 pharmacology & pharmacy Flow cytometry Renin-Angiotensin System Platelet reactivity Angiotensin Receptor Antagonists 03 medical and health sciences 0302 clinical medicine Thrombin receptor medicine Humans Pharmacology (medical) Platelet cardiovascular diseases 030212 general & internal medicine Receptor Ace inhibition Aged Aged 80 and over medicine.diagnostic_test Chemistry Thrombin General Medicine Middle Aged Flow Cytometry Blockade Female |
| Zdroj: | European Journal of Clinical Pharmacology. 76:1245-1251 |
| ISSN: | 1432-1041 0031-6970 |
| Popis: | ACE inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are important drugs in cardiovascular disease. However, little is known about which of these drug class is to be preferred. First analyses show that the blockade of the renin-angiotensin-aldosterone system (RAAS) influences platelet reactivity. Therefore, we evaluated the effects of ACEI and ARB on platelet reactivity and thrombin generation. We conducted a time series analysis in 34 patients. We performed light transmission aggregometry (LTA) to evaluate platelet reactivity. Results are given as maximum of aggregation (MoA). Thrombin generation was measured as endogenous thrombin potential (ETP) via calibrated automated thrombogram. Flow cytometry was used to analyze protease-activated receptor (PAR)-1 expression. ACEI treatment significantly increased platelet reactivity already 4 h after initiation of treatment (prior vs. 4 h post ACEI: MoA 41.9 ± 16.2% vs. 55.2 ± 16.7%; p = 0.003). After switching from ACEI to ARB treatment, platelet reactivity decreased significantly (3 months after switching: MoA 34.7 ± 20.9%; p = 0.03). ACEI reduced endogenous thrombin potential significantly from before to 3 months after ACEI (ETP 1527 ± 437 nM × min vs. 1088 ± 631 nM × min; p = 0.025). Platelet thrombin receptor (PAR1) expression increased from 37.38 ± 10.97% before to 49.53 ± 6.04% after ACEI treatment (p = 0.036). ACEI enhanced platelet reactivity. This can be reversed by changing to ARB. The mechanism behind RAAS influencing platelet function seems to be associated with PAR-1 expression. |
| Databáze: | OpenAIRE |
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