News Column

Studies by I.B. Gubrij and Co-Authors Describe New Findings in Gene Therapy (Attenuation of Monocrotaline-Induced Pulmonary Hypertension by Luminal...

July 29, 2014



Studies by I.B. Gubrij and Co-Authors Describe New Findings in Gene Therapy (Attenuation of Monocrotaline-Induced Pulmonary Hypertension by Luminal Adeno-Associated Virus Serotype 9 Gene Transfer of Prostacyclin Synthase)

By a News Reporter-Staff News Editor at Life Science Weekly -- Investigators discuss new findings in Biotechnology. According to news reporting out of Little Rock, Arkansas, by NewsRx editors, research stated, "Idiopathic pulmonary arterial hypertension (iPAH) is associated with high morbidity and mortality. We evaluated whether luminal delivery of the human prostacyclin synthase (hPGIS) cDNA with adeno-associated virus (AAV) vectors could attenuate PAH."

Our news journalists obtained a quote from the research, "AAV serotype 5 (AAV5) and AAV9 vectors containing the hPGIS cDNA under the control of a cytomegalovirus-enhanced chicken -actin (CB) promoter or vehicle (saline) were instilled into lungs of rats. Two days later, rats were injected with monocrotaline (MCT, 60mg/kg) or saline. Biochemical, hemodynamic, and morphologic assessments were performed when the rats developed symptoms (3-4 weeks) or at 6 weeks. Luminal (airway) administration of AAV5 and AAV9CBhPGIS vectors (MCT-AAV5 and MCT-AAV9 rats) significantly increased plasma levels of 6-keto-PGF1 as compared with MCT-controls, and closely resembled levels measured in rats not treated with MCT (saline-saline). Right ventricular (RV)/left ventricular (LV)+septum (S) ratios and RV systolic pressure (RVSP) were greater in MCT-control rats than in saline-saline rats, whereas the ratios and RVSP in MCT-AAV5CBhPGIS and MCT-AAV9CBhPGIS rats were similar to saline-saline rats. Thickening of the muscular media of small pulmonary arteries of MCT-control rats was detected in histological sections, whereas the thickness of the muscular media in MCT-AAV5CBhPGIS and MCT-AAV9CBhPGIS rats was similar to saline-saline controls. In experiments with different promoters, a trend toward increased levels of PGF1 expression was detected in lung homogenates, but not plasma, of MCT-treated rats transduced with an AAV9-hPGIS vector containing a CB promoter. This correlated with significant reductions in the RV/LV+S ratio and RVSP in MCT-AAV9CBhPGIS rats that resembled levels in saline-saline rats. No changes in levels of PGF1, RV/LV+S, or RVSP were detected in rats transduced with AAV9-hPGIS vectors containing a modified CB promoter (CB7) or a distal epithelial cell-specific promoter (CC10)."

According to the news editors, the research concluded: "Thus, AAV9CBhPGIS vectors prevented development of MCT-induced PAH and associated pulmonary vascular remodeling."

For more information on this research see: Attenuation of Monocrotaline-Induced Pulmonary Hypertension by Luminal Adeno-Associated Virus Serotype 9 Gene Transfer of Prostacyclin Synthase. Human Gene Therapy, 2014;25(6):498-505. Human Gene Therapy can be contacted at: Mary Ann Liebert, Inc, 140 Huguenot Street, 3RD Fl, New Rochelle, NY 10801, USA. (Mary Ann Liebert, Inc. - www.liebertpub.com; Human Gene Therapy - www.liebertpub.com/overview/human-gene-therapy-and-part-b-methods/19/)

Our news journalists report that additional information may be obtained by contacting I.B. Gubrij, Univ Arkanas Med Sci, Coll Med, Div Physiol & Biophys, Little Rock, AR 72205, United States. Additional authors for this research include S.R. Martin, A.K. Pangle, R. Kurten and L.G. Johnson (see also Biotechnology).

Keywords for this news article include: Little Rock, Arkansas, United States, North and Central America, Biotechnology, Enzymes and Coenzymes, Synthase

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


For more stories covering the world of technology, please see HispanicBusiness' Tech Channel



Source: Life Science Weekly


Story Tools






HispanicBusiness.com Facebook Linkedin Twitter RSS Feed Email Alerts & Newsletters