抗アポプトシス因子Bcl-2のウイルスの遺伝子転送は,慢性的な後発血性心不全から保護します

Subhasis Chatterjee¹, Allan S Stewart, Lawrence T Bish

¹Division of Cardiothoracic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pa 19104, USA.

Circulation

|October 2, 2002

まとめ

Bcl-2の遺伝子転送は,アポトーシスとリモデリングを減らすことで,発血後の心臓機能と構造を効果的に保ち,発血後の心不全の潜在的な治療法を提供します.

科学分野:

心血管科学の研究について
遺伝子療法の遺伝子治療法
分子心臓病学分子心臓病学

背景:

アポトーシスは,イシュケミアと慢性的な改造後の心不全に寄与します.
Bcl-2のウイルスの遺伝子転送は,アポトーシスをブロックし,心臓の機能を保存することを目的としています.

研究の目的:

アデノ-Bcl-2遺伝子移植の有効性を評価し,アポトーシスを予防し,心室の幾何学と機能を保存する.
心臓のリモデリングと心不全の進行に対するBcl-2遺伝子転送の長期的な効果を評価する.

主な方法:

地域性イシュケミア-再輸血のウサギモデルを使用した.
実験グループはアデノ-Bcl-2を投与し,対照群はアデノ-nullを投与した.
心臓機能はエコーカルディオグラフィとソノミクロメトリーで評価され,アポトーシスと心室改造は6週間で評価された.

主要な成果:

Bcl-2で治療されたウサギは,イシュケミア後2,4,6週間で,より高いエジェクション分数と上部境界地帯の分数縮小を維持しました.
左心室 (LV) の幾何学が著しく保たれ,Bcl-2グループでは拡張と壁の薄れが減少した.
Bcl-2グループと対照群の比較では,アポトーシスの減少と心室の改造が観察され,3日目に急性機能的差異は認められなかった.

結論:

In vivoのBcl-2の遺伝子転送は,イシュケミアの後のLVの機能と幾何学を保ち,後期ポストイシュケミアの心不全に対する潜在的な治療戦略を示しています.
6週間の観察された効果は,Bcl-2-媒介によるアポトーシスの減少と,その後の心室リモデリングに起因する.
Adeno-Bcl-2の投与は,心不全の進行を緩和する有望なアプローチを示しています.

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