title: The Multifaceted Clinical Readouts of Platelet Inhibition by Low-Dose Aspirin.
abstract: Inactivation of platelet cyclooxygenase (COX)-1 by low-dose aspirin leads to long-lasting suppression of thromboxane (TX) A2 production and TXA2-mediated platelet activation and aggregation. This effect is necessary and sufficient to explain aspirin's unique (among other COX-1 inhibitors) effectiveness in preventing atherothrombosis, as well as its shared (with other antiplatelet agents) bleeding liability. However, different mechanisms of action have been suggested to explain other beneficial effects of aspirin, such as prevention of venous thromboembolism, chemoprevention of colorectal (and other) cancers, and reduced risk of dementia. These mechanisms include acetylation of other proteins in blood coagulation, inhibition of COX-2 activity, and other COX-independent mechanisms. The intent of this review is to develop the concept that the multifaceted therapeutic effects of low-dose aspirin may reflect pleiotropic consequences of platelet inhibition on pathophysiological tissue repair processes. Furthermore, the clinical implications of this concept will be discussed in terms of current clinical practice and future research.
authors.affiliation: Department of Pharmacology, Catholic University School of Medicine, Rome, Italy. Electronic address: carlo.patrono@rm.unicatt.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Patrono
mesh_terms: D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention; D015179:Colorectal Neoplasms / Q000517:prevention & control; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015140:Dementia, Vascular / Q000517:prevention & control; D006801:Humans; D014652:Vascular Diseases / Q000517:prevention & control*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D001241:Aspirin
keywords: atherothrombosis; colorectal cancer; platelet COX-1; venous thromboembolism