Highly efficient liposome-mediated gene transfer of inducible nitric oxide synthase in vivo and in vitro in vascular smooth muscle cells.
Objective: The efficient introduction of regulatory genes into vascular smooth muscle cells (SMCs) is one of the most promising options for gene therapy of cardiovascular diseases. Cationic liposome-mediated gene transfer may become a favorable transfection technique with regard to patient’s safety for in vivo administration. However, this method until now has its limitation in a low transfection efficiency. Therefore, the present study was designed to improve cationic liposome-mediated transfection of rabbit vascular SMCs in vitro and in vivo, in order to enhance transfection efficiency and present an optimized system which may offer a potential therapeutic benefit for in vivo application.…
Involvement of PKC and NF-κB in Nitric Oxide Induced Apoptosis in Human Coronary Artery Smooth Muscle Cells
Apoptosis of vascular smooth muscle cells is critically involved in progression of atherosclerosis and may prevent intimal hyperplasia in restenosis and vascular remodeling. Nitric oxide (NO) is known to induce apoptosis, but the signaling pathways still remain unclear. We investigated p53 accumulation, protein kinase C (PKC) activation and nuclear transcription factor (NF-kappaB) binding activity as possible signaling mechanisms of NO-induced apoptosis. Apoptosis was induced dose-dependently with the NO-donors sodiumnitroprusside (SNP: 232+/-48%) and SIN-1 (241+/-90% of actinomycin D induced apoptosis; means +/- SEM, *por =0.05 vs. control) in HSMC. Inhibition of PKC significantly attenuat…
NO Reduces PMN Adhesion to Human Vascular Endothelial Cells Due to Downregulation of ICAM-1 mRNA and Surface Expression
Reperfusion damage is largely due to the adherence of polymorphonuclear leukocytes to the endothelium initiated by adhesion molecule upregulation. The reduced endothelial nitric oxide release during ischemia may be involved in the upregulation of intercellular adhesion molecule 1. In this study, we tested if nitric oxide donors suppress polymorphonuclear leukocyte adherence to activated endothelial cells by inhibition of the intercellular adhesion molecule 1 surface expression. Confluent human umbilical vein endothelial cells were stimulated with tumor necrosis factor alpha (300 U/mL) after preincubation with increasing concentrations of the nitric oxide donors CAS 1609 (0.005-5 mM/L) and 3…
Lokale Medikamentengabe und Gentherapie
Eines der wichtigsten Probleme der klinischen Kardiologie, die Entwickung einer Restenose nach koronarer Ballonangioplastie, ist bisher noch nicht befriedigend gelöst. Die pathophysiologischen Erkenntnisse über die Mechanismen der Neointimabildung sind noch unvollständig, und zahlreiche Therapiestudien mit systemisch applizierten Pharmaka mit unterschiedlichem Wirkungsmechanismus sind fehlgeschlagen. Mögliche innovative Therapieansätze betreffen die hochdosierte lokale Substanzapplikation an der Dilatationsstelle und lokale gentherapeutische Eingriffe zur Verhinderung der Neointimabildung durch Proliferationshemmung der glatten Gefäßmuskelzellen. Zahlreiche Kathetermodelle sind entwickelt w…