Tetsuya Nakakuki

Rho/Rho-Kinase Pathway Contributes to C-Reactive Protein–Induced Plasminogen Activator Inhibitor-1 Expression in Endothelial Cells

Objective—Rho/Rho-kinase pathway plays pivotal roles in cardiovascular diseases including arteriosclerosis and hypertension. Recently it has become evident that C-reactive protein (CRP), a powerful marker for cardiovascular events, has direct proatherothrombotic effects on vascular cells. However, its molecular mechanism has not been fully investigated. We examined the involvement of Rho/Rho-kinase signaling in CRP-induced plasminogen activator inhibitor-1 (PAI-1) expression in bovine aortic endothelial cells (BAECs). Methods and Results—PAI-1 expression was determined by Western blotting. RhoA activation was determined by an affinity pull-down assay using Rho-binding fragment of rhotekin. NF-&kgr;B activity was determined using the luciferase reporter gene. Incubation of BAECs with human recombinant CRP (≥25 &mgr;g/mL) induced a significant increase in PAI-1 expression. Stimulation of BAECs with CRP significantly increased RhoA activation. Pretreatment with TAT-C3 (a membrane-permeable RhoA inhibitor) and Y-27632 (Rho-kinase inhibitor) significantly inhibited CRP-induced PAI-1 expression. NF-&kgr;B activity was markedly enhanced by CRP and pretreatment with Y-27632 inhibited its activation. Parthenolide, SN50, and BAY 11-7082 (NF-&kgr;B inhibitors) significantly blocked CRP-mediated PAI-1 expression. Conclusions—These data suggested that CRP activates Rho/Rho-kinase signaling, which in turn activates NF-&kgr;B activity, resulting in PAI-1 expression in BAEC. These observations provide evidence for the possible involvement of Rho/Rho-kinase signaling in CRP-induced atherothrombogenesis.

A case of primary cardiac lymphoma located in the pericardial effusion

Primary cardiac lymphoma is a rare disorder with a poor prognosis. We present here a case of 77-year-old woman who was diagnosed as having cardiac lymphoma antemortem according to a cytologic examination of the pericardial effusion. Determination of the levels of serum-soluble interleukin-2 receptor and serum deoxythymidine kinase was useful for the diagnosis. Echocardiography, computed tomography, magnetic resonance imaging, and gallium scan revealed neither lymphadenopathy nor tumor in the heart, so she was diagnosed as having malignant lymphoma that probably originated from the pericardium. Systemic chemotherapy with CHOP (cyclophosphamide, farmorubicin, oncovin, and prednisolone) resulted in a complete resolution of the pericardial effusion. She has been in remission 48 months after discontinuation of the chemotherapy.