Pulmonary Vascular Disease |

Plasmid-Based Short Hairpin RNA Against Connective Tissue Growth Factor Attenuated Monocrotaline-Induced Pulmonary Vascular Remodeling in Rats FREE TO VIEW

Ran Wang; Sijing Zhou; Daxiong Zeng; Gengyun Sun
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Anhui Medical University, Hefei, China

Chest. 2014;146(4_MeetingAbstracts):858A. doi:10.1378/chest.1992117
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SESSION TITLE: DVT/PE/Pulmonary Hypertension

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 29, 2014 at 07:30 AM - 08:30 AM

PURPOSE: Pulmonary hypertension is a life-threatening medical condition, and a growing body of evidence shows that the expression of connective tissue growth factor (CTGF) is significantly associated with its pathogenesis, making it an attractive therapeutic target. Our earlier work revealed intravenously administered plasmid-based CTGF-specific short hairpin RNA (shRNA) could attenuate pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling in rats exposed to cigarette smoke.The aim of the present study was to explore the therapeutic role of this shRNA plasmid in the treatment of monocrotaline-induced pulmonary vascular remodeling in rats.

METHODS: The animal model of pulmonary artery remodeling was established by a single injection of monocrotaline in rats, and the upregulation of CTGF in PASMCs was semi-quantified by using western blot. CTGF specific shRNA was mixed with EXGEN500/Glucose prior to intratracheal administration, and transfection efficiency as well as the distribution in lung tissues was evaluated using western blot and fluorescence immunostaining.

RESULTS: We showed that GFP expression was significantly higher in shRNA-treated rats than the control, and the GFP was mainly expressed in pulmonary vessels, airways, and mesenchyme. Additionally, the upregulation of CTGF could be attenuated by intratracheal administration of the shRNA, and accordingly, this shRNA was found to be able to repress monocrotaline-induced pulmonary vascular remodeling, as evidenced by its ability to reduce the percentage of muscularized vessels and the wall thickness of pulmonary vessels.

CONCLUSIONS: We concluded that plasmid-based shRNA against CTGF attenuated pulmonary vascular remodeling in monocrotaline-treated rats. CTGF might be a potential target for the treatment of pulmonary vascular remodeling and pulmonary hypertension.

CLINICAL IMPLICATIONS: shRNA has been reported to be intratracheally given to successfully treat lung disease, and shRNA/EXGEN500 is a nucleic acids delivery method with high transfection efficiency and low toxicity, which has been intratracheally administered to treat different pulmonary diseases by knocking-down another target gene in experimental animals and the efficacy was satisfactory. Considering the fact that there are few therapeutic options to treat pulmonary hypertension, this study presented an interesting and promising way to treat the disease.

DISCLOSURE: The following authors have nothing to disclose: Ran Wang, Sijing Zhou, Daxiong Zeng, Gengyun Sun

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