AAV-PGIS gene transfer improves hypoxia-induced pulmonary hypertension in mice

Kawakami, Takashi; Satoh, Tsuyoshi; Ieda, Masaki; Ieda, Yasuyo; Kimura, Kensuke; Mochizuki, Hideki; Shimada, Takashi; Yokoyama, Chieko; Ogawa, Satoshi; Tanabe, Tadashi; Fukuda, Keiichi

doi:10.1016/j.bbrc.2007.09.039

Cited by 13 publications

(15 citation statements)

References 16 publications

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“…4C and D), which are consistent with data from Hadri et al (2013) (Pan et al, 1993). Despite these strain differences, the data presented from our study compare favorably to the data from the intramuscular injection of AAV1 and AAV2-hPGIS vectors and luminal airway aerosol administration of AAV-SERCA2 vectors in a prevention of MCT-induced PAH model (Ito et al, 2007;Kawakami et al, 2007;Hadri et al, 2013;Kataoka et al, 2013).…”

supporting

confidence: 80%

“…Prior studies of intramuscular injection of AAV1 and AAV2-hPGIS vectors also used a prevention model approach (Ito et al, 2007;Kawakami et al, 2007;Kataoka et al, 2013). In contrast, Hadri et al (2013) administered an AAV1-SER-CA2 vector by luminal airway aerosol administration with a Penn Century Device in both prevention and established MCT-PAH models with similar results.…”

mentioning

confidence: 62%

“…Intratracheal and direct hepatic injections of the hemagglutinating virus of Japan (HVJ)-PGIS liposomes have confirmed this concept (Ono et al, 2004). Delivery of adeno-associated virus serotype 1 (AAV1)-and AAV2-hPGIS vectors by intramuscular injection has been shown to attenuate monocrotaline (MCT)-induced and chronic hypoxic PAH in rodents (Ito et al, 2007;Kawakami et al, 2007;Kataoka et al, 2013). Recently, attenuation of established MCT-induced PAH by aerosolized airway luminal delivery of AAV1-SERCA2 with a Penn Century Device has been reported (Hadri et al, 2013).…”

mentioning

confidence: 69%

“…Limberis and Wilson, 2006;Limberis et al, 2009). Previous studies of AAV-hPGIS vectors in chronic hypoxic mice or MCT-treated rats relied extensively on the AAV1 and AAV2 serotype vectors delivered by intramuscular injection (Ito et al, 2007;Kawakami et al, 2007;Kataoka et al, 2013). While AAV1 has been used for lung gene transfer, its utility in muscle gene transfer has been recognized in many fields of clinical gene transfer (Song et al, 1998;Chao et al, 2000;Flotte et al, 2011).…”

mentioning

confidence: 99%

“…One of the hallmarks of the prior in vivo gene transfer studies with AAV-hPGIS vectors was the consistent selection of the CB or CAG promoters to drive transcription of the hPGIS cDNA (Ito et al, 2007;Kawakami et al, 2007;Kataoka et al, 2013). We tested the CB promoter against a modified version of the CB promoter known as CB7 (provided by the Penn Vector Core) and against the epithelialspecific promoter, CC10 (Stripp et al, 1992;Auricchio et al, 2002).…”

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confidence: 99%

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Attenuation of Monocrotaline-Induced Pulmonary Hypertension by Luminal Adeno-Associated Virus Serotype 9 Gene Transfer of Prostacyclin Synthase

et al. 2014

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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. AAV serotype 5 (AAV5) and AAV9 vectors containing the hPGIS cDNA under the control of a cytomegalovirus-enhanced chicken b-actin (CB) promoter or vehicle (saline) were instilled into lungs of rats. Two days later, rats were injected with monocrotaline (MCT, 60 mg/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 a as compared with MCTcontrols, 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 MCTcontrol rats than in saline-saline rats, whereas the ratios and RVSP in MCT-AAV5CBhPGIS and MCTAAV9CBhPGIS 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 a 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 a , RV/LV + S, or RVSP were detected in rats transduced with AAV9-hPGIS vectors containing a modified CB promoter (CB7) or a distal epithelial cellspecific promoter (CC10). Thus, AAV9CBhPGIS vectors prevented development of MCT-induced PAH and associated pulmonary vascular remodeling.

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confidence: 80%

mentioning

confidence: 62%

mentioning

confidence: 69%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Attenuation of Monocrotaline-Induced Pulmonary Hypertension by Luminal Adeno-Associated Virus Serotype 9 Gene Transfer of Prostacyclin Synthase

et al. 2014

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Targeted Delivery of Genes to Endothelial Cells and Cell‐ and Gene‐Based Therapy in Pulmonary Vascular Diseases

Suen

Mei

Kugathasan

et al. 2013

Comprehensive Physiology

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Pulmonary arterial hypertension (PAH) is a devastating disease that, despite significant advances in medical therapies over the last several decades, continues to have an extremely poor prognosis. Gene therapy is a method to deliver therapeutic genes to replace defective or mutant genes or supplement existing cellular processes to modify disease. Over the last few decades, several viral and nonviral methods of gene therapy have been developed for preclinical PAH studies with varying degrees of efficacy. However, these gene delivery methods face challenges of immunogenicity, low transduction rates, and nonspecific targeting which have limited their translation to clinical studies. More recently, the emergence of regenerative approaches using stem and progenitor cells such as endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have offered a new approach to gene therapy. Cell-based gene therapy is an approach that augments the therapeutic potential of EPCs and MSCs and may deliver on the promise of reversal of established PAH. These new regenerative approaches have shown tremendous potential in preclinical studies; however, large, rigorously designed clinical studies will be necessary to evaluate clinical efficacy and safety.

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Type 2 inositol 1,4,5-trisphosphate receptor inhibits the progression of pulmonary arterial hypertension via calcium signaling and apoptosis

et al. 2018

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AAV-PGIS gene transfer improves hypoxia-induced pulmonary hypertension in mice

Cited by 13 publications

References 16 publications

Attenuation of Monocrotaline-Induced Pulmonary Hypertension by Luminal Adeno-Associated Virus Serotype 9 Gene Transfer of Prostacyclin Synthase

Attenuation of Monocrotaline-Induced Pulmonary Hypertension by Luminal Adeno-Associated Virus Serotype 9 Gene Transfer of Prostacyclin Synthase

Targeted Delivery of Genes to Endothelial Cells and Cell‐ and Gene‐Based Therapy in Pulmonary Vascular Diseases

Type 2 inositol 1,4,5-trisphosphate receptor inhibits the progression of pulmonary arterial hypertension via calcium signaling and apoptosis

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