Letter by Strande Regarding Article “Protease-Activated Receptor-1 Contributes to Cardiac Remodeling and Hypertrophy”

The authors showed that protease-activated receptor-1 (PAR-1)-deficient mice had preservation of left ventricular size and function after myocardial ischemia and reperfusion (IR) injury when compared with wild-type littermates.Conversely, PAR-1-deficient mice did not have a decreased myocardial infarct size after IR injury.The authors then went on to show that mice selectively overexpressing PAR-1 in cardiomyocytes developed left ventricular dilatation and dysfunction when compared with wild-type littermates.This is very exciting data with great translational potential, especially when considering the ongoing clinical development of a PAR-1 antagonist for other indications (ClinicalTrials.govIdentifier: NCT00526474).My concern for the translational potential of their study regards their observation that PAR-1 deficiency in mice did not protect against acute myocardial IR injury.We have previously shown that a competitive inhibitor of PAR-1 (SCH 79797) protects the rat heart against acute IR injury. 2 The authors 1 explain this discrepancy by