Effects of Adenovirus-Mediated Delivery of the Human Hepatocyte Growth Factor Gene in Experimental Radiation-Induced Heart Disease

Journal Article · Tue Dec 01 00:00:00 EST 2009 · International Journal of Radiation Oncology, Biology and Physics

OSTI ID:21367567

Shunying, Hu; Yundai, Chen ^[1]; Libing, Li ^[2]; Jinlong, Chen; Bin, Wu ^[3]; Zhou, Xiao; Guang, Zhi ^[1]; Qingfang, Li; Rongliang, Wang; Haifeng, Duan; Zikuan, Guo; Yuefeng, Yang; Fengjun, Xiao ^[3]; Lisheng, Wang ^[3]

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1. Department of Cardiology, Chinese PLA General Hospital, Beijing (China)
2. Department of Cardiovascular Surgery, Chinese PLA General Hospital, Beijing (China)
3. Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing (China)

Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 +- 9.01 vs. 41.94 +- 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 +- 1303 vs. 1667 +- 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 +- 1084 vs. 1566 +- 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.

• OSTI ID: 21367567
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 75, Issue 5; Other Information: DOI: 10.1016/j.ijrobp.2009.07.1697; PII: S0360-3016(09)02804-1; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
ADENOVIRUS
BLOOD FLOW
CARDIOVASCULAR DISEASES
FIBROSIS
GAMMA RADIATION
GENE THERAPY
GENES
GROWTH FACTORS
HEART
LIVER CELLS
RATS
ANIMAL CELLS
ANIMALS
BODY
CARDIOVASCULAR SYSTEM
DISEASES
ELECTROMAGNETIC RADIATION
IONIZING RADIATIONS
MAMMALS
MEDICINE
MICROORGANISMS
MITOGENS
ONCOGENIC VIRUSES
ORGANIC COMPOUNDS
ORGANS
PARASITES
PATHOLOGICAL CHANGES
PROTEINS
RADIATIONS
RODENTS
SOMATIC CELLS
THERAPY
VERTEBRATES
VIRUSES