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Cardiovascular Side Effects of Vioxx Potentially Identified

Study suggests the drug increases the production of a protein that initiates blood coagulation

TUESDAY, Aug. 28 (HealthDay News) -- Cyclooxygenase-2 (COX-2) inhibitors such as Vioxx increase the production of a protein that initiates blood coagulation, possibly explaining the cardiovascular side effects associated with these drugs, according to the results of a study published online Aug. 27 in the Journal of Experimental Medicine.

Timothy Hla, Ph.D., from the University of Connecticut Health Center in Farmington, and colleagues examined the downstream signaling effects of treating cells with COX-2 substrates and inhibitors.

The researchers found that COX-2 substrates led to a decrease in the expression of tissue factor (TF), a primary initiator of blood coagulation. COX-2 inhibitors blocked this decrease, inducing TF expression in vascular endothelium and elevating circulating TF activity in mice. TF inhibitors could reduce these elevated TF levels in mice, the authors note.

"We provide evidence that COX-2-dependent attenuation of TF expression is abrogated by COX-2 inhibitors, which may explain the prothrombotic side-effects for this class of drugs," Hla and colleagues conclude.

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