Ex vivo adenovirus-mediated gene transfer to the adult rat heart
Ex vivo adenovirus-mediated gene transfer to the adult rat heart
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DOI：
10.1016/s0022-5223(98)70327-7
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发表时间：
1998-03-01
影响因子：
6
通讯作者：
Koch, WJ
中科院分区：
文献类型：
--
作者：
Kypson, AP;Peppel, K;Koch, WJ
Objective: The ability to transfer genes to adult myocardium may have therapeutic implications for cardiac transplantation. We investigated the feasibility of adenovirus-mediated transfer of marker genes LacZ and Luciferase, as well as the potentially therapeutic gene of the human beta(2)-adrenergic receptor in a rat heterotopic heart transplant model. Methods: Donor hearts were flushed with 10(12) total viral particles of one of three transgenes. Hearts were harvested at various time points after transplantation. LacZ-treated hearts were assessed by histologic staining and Luciferase-treated hearts were assayed for specific luminescence activity. Hearts treated with beta(2)-adrenergic receptor underwent radioligand binding assays and immunohistochemistry with the use of an antibody specific for the human beta(2)-adrenergic receptor. Results: LacZ hearts revealed diffuse myocyte staining as opposed to none within controls at 5 days. Luciferase hearts demonstrated a mean activity of 970,000 +/- 220,000 arbitrary light units versus 500 +/- 200 for the controls (p = 0.001). Total beta(2)-adrenergic receptor densities (fmol/mg membrane protein) for hearts that received the beta(2)-adrenergic receptor transgene at 3, 5, 7, 10, and 14 days after infection were as follows: right ventricle, 488.5 +/- 126.8, 519.4 +/- 81.8,* 477.1 +/- 51.8,* 183.0 +/- 6.5,* and 82.7 +/- 19.1; left ventricle, 511.0 +/- 167.6, 1206.4 +/- 321.8,* 525.3 +/- 188.7, 183.5 +/- 18.6,* and 75.9 +/- 15.2 (*p < 0.05 vs control value of 75.6 +/- 6.4). Immunohistochemical analysis revealed diffuse staining of varying intensity within myocardial sarcolemmal membranes. Conclusions: We conclude that global overexpression of different transgenes is possible during cardiac transplantation and, ultimately, adenovirus-mediated gene transfer map provide a unique opportunity for genetic manipulation of the donor organ, potentially enhancing its function.
