Viral Gene Transfer of the Antiapoptotic Factor Bcl-2 Protects Against Chronic Postischemic Heart Failure
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- Subhasis Chatterjee
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
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- Allan S. Stewart
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
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- Lawrence T. Bish
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
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- Vasant Jayasankar
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
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- Elizabeth M. Kim
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
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- Timothy Pirolli
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
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- Jeffrey Burdick
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
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- Y. Joseph Woo
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
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- Timothy J. Gardner
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
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- H. Lee Sweeney
- From the Division of Cardiothoracic Surgery (S.C., A.S.S., V.J., J.B., J.W., T.J.G.) and the Department of Physiology (L.T.B., E.M.K., T.P., H.L.S.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
抄録
<jats:p> <jats:bold> <jats:italic>Background</jats:italic> </jats:bold> Apoptosis secondary to acute ischemia and chronic remodeling is implicated as a mediator of heart failure. This study was designed to assess the effect of in vivo viral gene transfer of the anti-apoptotic factor Bcl-2 to block apoptosis and preserve ventricular geometry and function. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results</jats:italic> </jats:bold> In a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adeno-Bcl-2 was compared with a control group receiving empty vector adeno-null. Function was assessed by echocardiography, and sonomicrometry of the border zone was compared with the normal left ventricle (LV). Animals were killed at 6 weeks, and an additional group was killed after 3 days to see whether virus administration conferred an immediate effect. Animals that were administered Bcl-2 maintained higher ejection fractions at 2, 4, and 6 weeks compared with controls. Sonomicrocrystals demonstrated greater protection of border zone fractional shortening at 6 weeks. The Bcl-2 group had superior preservation of LV geometry with less ventricular dilatation and wall thinning. There was also reduced apoptosis compared with the controls. Finally, in the animals killed at 3 days, no functional difference was observed between the Bcl-2 and control groups. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions</jats:italic> </jats:bold> Gene transfer of Bcl-2 preserves LV function after ischemia despite the absence of an observed acute protective effect. The benefit at 6 weeks is postulated to result from a Bcl-2–mediated reduction in apoptosis and ventricular remodeling. Adeno–Bcl-2 administration offers a potential strategy to protect the heart from late postischemic heart failure. </jats:p>
収録刊行物
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- Circulation
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Circulation 106 (12_suppl_1), I212-, 2002-09-24
Ovid Technologies (Wolters Kluwer Health)