title: Aspirin delimits platelet life span by proteasomal inhibition.
abstract: Aspirin is widely used in clinical settings as an anti-inflammatory and anti-platelet drug due its inhibitory effect on cyclooxygenase activity. Although the drug has long been considered to be an effective and safe therapeutic regime against inflammatory and cardiovascular disorders, consequences of its cyclooxygenase-independent attributes on platelets, the key players in thrombogenesis, beg serious investigation. In this report we explored the effect of aspirin on platelet lifespan in murine model and its possible cytotoxicity against human platelets in vitro. Aspirin administration in mice led to significant reduction in half-life of circulating platelets, indicative of enhanced rate of platelet clearance. Aspirin-treated human platelets were found to be phagocytosed more efficiently by macrophages, associated with attenuation in platelet proteasomal activity and upregulation of conformationally active Bax, which were consistent with enhanced platelet apoptosis. Although the dosage of aspirin administered in mice was higher than the therapeutic regimen against cardiovascular events, it is comparable with the recommended anti-inflammatory prescription. Thus, above observations provide cautionary framework to critically re-evaluate prophylactic and therapeutic dosage regime of aspirin in systemic inflammatory as well as cardiovascular ailments.
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Manasa K
authors.initials: MK
authors.lastname: Nayak
authors.affiliation: Indian Institute of Science Education and Research, Kolkata, India.
authors.forename: Ayusman
authors.initials: A
authors.lastname: Dash
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Nitesh
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Dash
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex; D001241:Aspirin