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The translational therapeutics of prostaglandin inhibition in atherothrombosis
Author(s) -
YU Y.,
RICCIOTTI E.,
GROSSER T.,
FITZGERALD G. A.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03439.x
Subject(s) - medicine , prostaglandin , pharmacology , posttranslational modification , translational medicine , chemistry , biochemistry , pathology , enzyme
Summary. Prostaglandins, products of the cyclo‐oxygenase (COX) enzymes, can both promote and restrain atherothrombosis. While non‐steroidal anti‐inflammatory drugs (NSAIDs) selective for inhibition of COX‐2 predispose to myocardial infarction, heart failure, hypertension and stroke, suppression of products of COX‐1, such as thromboxane (Tx) A 2 , underlie cardioprotection from low‐dose aspirin. Data from clinical pharmacology, rodent models, human genetics, observational studies and randomized trials provide insight into the implications of inhibiting COX product synthesis or function. Many lines of evidence afford a mechanistic explanation for the cardiovascular (CV) hazard from NSAIDs. Elucidation of the biology of this pathway using diversified approaches is also relevant to understanding the implications of substrate rediversion following inhibition of enzymes downstream of COXs, such as the microsomal PGE synthase (mPGES)‐1 and of combining D prostanoid antagonism with niacin to attenuate facial flushing.