[Gene therapy for pulmonary hypertension].
Pulmonary hypertension is a life-threatening disease characterized by progressive vascular remodeling, ultimately producing right ventricular failure. Recently, continuous intravenous infusion of prostacyclin has become recognized as a therapeutic breakthrough that can improve hemodynamics and surgical in patients with pulmonary hypertension. Nevertheless, gene therapy is also expected as a valuable therapeutic approach in pulmonary hypertension for the reason that transgene expression is located mainly in the lung. Previous study demonstrated that intratracheal gene transfer of endothelial derived nitric oxide synthase, prostacyclin I synthase, vascular endothelial growth factor etc. resulted in a reduction of pulmonary arterial pressure in experimental animals with pulmonary hypertension. Major hurdle in current gene therapy for pulmonary hypertension may be the limited duration of transgene expression in lung tissue. However, rather than a limitation, this feature may be a advantage in some situations where expression during only a few weeks may provide both adequate therapeutic efficacy and limited side effects. Development of second-generation gene delivery system will provide new tools to prolong the duration of transgene expression.
Setoguchi
Y
Y
Department of Respiratory Medicine, Juntendo University School of Medicine.
Fukuchi
Y
Y
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics; D011464:Epoprostenol / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D006976:Hypertension, Pulmonary / Q000628:therapy*; D008222:Lymphokines / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D011464:Epoprostenol; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D015740:Calcitonin Gene-Related Peptide