Redox regulation of human protease-activated receptor-2 by activated factor X.

Activated factor X (FXa) exerts coagulation-independent actions such as proliferation of vascular smooth muscle cells (SMCs) through the protease-activated receptors PAR-1 and PAR-2. Both receptors are upregulated upon vascular injury but the underlying mechanisms have not been defined. We examined if FXa regulates PAR-1 and PAR-2 in human vascular SMCs.

Regulation of protease-activated receptor-1 by vasodilatory prostaglandins via NFAT.

Aims: We recently reported that prostacyclin suppresses protease-activated receptor-1 (PAR-1) in human vascular smooth muscle cells (VSMC) via cyclic AMP and protein kinase A. This study examines the downstream mechanisms, particularly the role of nuclear factor of activated T-cells (NFAT).

Methods And Results: Human saphenous vein VSMC were exposed to phorbol 12-myristate 13-acetate (PMA) to induce endogenous cyclooxygenase-2-dependent prostaglandin generation.

Complete downmodulation of P-selectin glycoprotein ligand in monocytes undergoing apoptosis.

Objective: Apoptotic monocytes release membrane microparticles which may play a major role in thrombogenicity through a P-selectin glycoprotein ligand (PGSL-1)-mediated mechanism. We have studied systematically the regulation of PSGL-1 expression and function in apoptotic monocytic cells.

Methods And Results: PSGL-1 expression (flow cytometry, immunofluorescence microscopy, immunoblot) was virtually abolished in apoptotic monocytes by proteolytic shedding.

Human cyclooxygenase-1b is not the elusive target of acetaminophen.

A cyclooxygenase-1 splice variant (cyclooxygenase-1b), cloned from canine brain, was proposed to be an acetaminophen-sensitive enzyme. Unlike in canines, the retention of intron 1 in the human sequence results in a frame shift and predicts a truncation of the protein. We have sought to answer the question whether human cyclooxygenase-1b, if expressed, is a target of acetaminophen.

Cyclooxygenase COX-2a, a novel COX-2 mRNA variant, in platelets from patients after coronary artery bypass grafting.

There are two principal cyclooxygenase isoforms referred to as COX-1 and COX-2. Recently, COX-3 has been identified. We have demonstrated the expression of COX-2 in platelets from patients after coronary artery bypass grafting (CABG).