No impact of polymorphism in the phosphodiesterase 5A gene in Cavalier King Charles Spaniels on pimobendan‐induced inhibition of platelet aggregation response

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Název: No impact of polymorphism in the phosphodiesterase 5A gene in Cavalier King Charles Spaniels on pimobendan‐induced inhibition of platelet aggregation response
Autoři: Maria J. Reimann, Daniel N. Faisst, Mads Knold, Kathryn M. Meurs, Joshua A. Stern, Signe E. Cremer, Jacob E. Møller, Ingrid Ljungvall, Jens Häggström, Lisbeth H. Olsen
Zdroj: J Vet Intern Med
Journal of Veterinary Internal Medicine, Vol 37, Iss 6, Pp 2145-2156 (2023)
Reimann, M J, Faisst, D N, Knold, M, Meurs, K M, Stern, J A, Cremer, S E, Møller, J E, Ljungvall, I, Häggström, J & Olsen, L H 2023, ' No impact of polymorphism in the phosphodiesterase 5A gene in Cavalier King Charles Spaniels on pimobendan-induced inhibition of platelet aggregation response ', Journal of Veterinary Internal Medicine, vol. 37, no. 6, pp. 1947-2660 . https://doi.org/10.1111/jvim.16871
Informace o vydavateli: Wiley, 2023.
Rok vydání: 2023
Témata: Cyclic Nucleotide Phosphodiesterases, Type 5, dogs, Platelet Aggregation, Veterinary medicine, Heart Valve Diseases, heart disease, Clinical Science, platelet inhibition, 3. Good health, Dogs, genetic variation, SF600-1100, Animals, SMALL ANIMAL, Dog Diseases, light transmission aggregometry, pharmacogenetics
Popis: BackgroundA variant in the canine phosphodiesterase (PDE) 5A gene (PDE5A:E90K) is associated with decreased concentrations of circulating cyclic guanosine monophosphate (cGMP) and response to PDE5 inhibitor treatment. Pimobendan is a PDE inhibitor recommended for medical treatment of certain stages of myxomatous mitral valve disease (MMVD) in dogs.HypothesisPDE5A:E90K polymorphism attenuates the inhibitory effect of pimobendan on in vitro platelet aggregation and increases basal platelet aggregation in Cavalier King Charles Spaniels (CKCS). Selected clinical variables (MMVD severity, sex, age, hematocrit, platelet count in platelet‐rich plasma [PRP], and echocardiographic left ventricular fractional shortening [LV FS]) will not show an association with results.AnimalsFifty‐two privately owned CKCS with no or preclinical MMVD.MethodsUsing blood samples, we prospectively assessed PDE5A genotype using Sanger sequencing and adenosine diphosphate‐induced platelet aggregation response (area under the curve [AUC], maximal aggregation [MaxA], and velocity [Vel]) with and without pimobendan using light transmission aggregometry. Dogs also underwent echocardiography.ResultsPimobendan inhibited platelet function as measured by AUC, MaxA, and Vel at a concentration of 10 μM (P P Conclusions and Clinical ImportanceThe PDE5A:E90K polymorphism did not influence in vitro basal platelet aggregation response or the inhibitory effect of pimobendan on platelet aggregation in CKCS. Dogs with the PDE5A:E90K polymorphism did not appear to have altered platelet function or response to pimobendan treatment.
Druh dokumentu: Article
Other literature type
Popis souboru: application/pdf
Jazyk: English
ISSN: 1939-1676
0891-6640
DOI: 10.1111/jvim.16871
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/37743723
https://doaj.org/article/cd502d1817ad4c5a967b5c356fee7e03
https://pub.epsilon.slu.se/33077/
https://curis.ku.dk/ws/files/381929381/Veterinary_Internal_Medicne_2023_Reimann_No_impact_of_polymorphism_in_the_phosphodiesterase_5A_gene_in_Cavalier_King.pdf
Rights: CC BY NC ND
URL: http://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Přístupové číslo: edsair.doi.dedup.....c9df24cda785a3be8c51a6343bdb5ed5
Databáze: OpenAIRE
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Popis
Abstrakt:BackgroundA variant in the canine phosphodiesterase (PDE) 5A gene (PDE5A:E90K) is associated with decreased concentrations of circulating cyclic guanosine monophosphate (cGMP) and response to PDE5 inhibitor treatment. Pimobendan is a PDE inhibitor recommended for medical treatment of certain stages of myxomatous mitral valve disease (MMVD) in dogs.HypothesisPDE5A:E90K polymorphism attenuates the inhibitory effect of pimobendan on in vitro platelet aggregation and increases basal platelet aggregation in Cavalier King Charles Spaniels (CKCS). Selected clinical variables (MMVD severity, sex, age, hematocrit, platelet count in platelet‐rich plasma [PRP], and echocardiographic left ventricular fractional shortening [LV FS]) will not show an association with results.AnimalsFifty‐two privately owned CKCS with no or preclinical MMVD.MethodsUsing blood samples, we prospectively assessed PDE5A genotype using Sanger sequencing and adenosine diphosphate‐induced platelet aggregation response (area under the curve [AUC], maximal aggregation [MaxA], and velocity [Vel]) with and without pimobendan using light transmission aggregometry. Dogs also underwent echocardiography.ResultsPimobendan inhibited platelet function as measured by AUC, MaxA, and Vel at a concentration of 10 μM (P P Conclusions and Clinical ImportanceThe PDE5A:E90K polymorphism did not influence in vitro basal platelet aggregation response or the inhibitory effect of pimobendan on platelet aggregation in CKCS. Dogs with the PDE5A:E90K polymorphism did not appear to have altered platelet function or response to pimobendan treatment.
ISSN:19391676
08916640
DOI:10.1111/jvim.16871