アテロスクレロスの加速,大動脈動脈瘤の形成,およびアポリポプロテインE/内皮酸化窒素合成酵素のダブルノックアウトマウスにおける缺血性心疾患
P J Kuhlencordt1, R Gyurko, F Han
1Cardiovascular Research Center, Cardiology Division, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Circulation
|July 27, 2001
まとめ
内皮酸化窒素合成酵素 (eNOS) 欠乏症は,動脈硬化症を著しく加速させ,欧米の食生活をしているマウスの冠動脈疾患を引き起こす. これは,高血圧によるだけではなく,心不全と大動脈の合併症につながる.
科学分野:
- 心血管科学の研究について
- 動脈硬化症の病原性 病原性
- ミュライン・モデル
背景:
- 腸内酸化窒素合成酵素 (eNOS) は,血管の健康に役割を果たしています.
- 動脈硬化症は複雑な心血管疾患である.
- 動脈硬化に影響を与える遺伝的要因を理解することは極めて重要です.
研究 の 目的:
- 動脈硬化症の発達に対するeNOS欠乏の影響を調査する.
- ダブルノックアウト (apoE/eNOS-DKO) と対照 (apoE-KO) マウスの病変形成を比較する.
- eNOS欠乏症に関連する心血管合併症を特定するために.
主な方法:
- apoE/eNOS-DKOマウスとapoE-KOマウスの病変発達の比較.
- 16週間,西欧型の食事で動物を飼育する.
- 動脈硬化症,冠動脈硬化症,線維症,心臓機能,および大動脈の整合性の評価.
主要な成果:
- apoE/eNOS-DKOマウスは,apoE-KO対照群と比較して,病変部位 (93.6%の雄,59.2%の雌) が著しく増加した.
- DKO動物は,外周冠動脈硬化症,線維症,心臓機能障害 (LV壁の厚さ増加,断片的縮小の減少) を発症した.
- 男性DKOマウスは自発的な大動脈動脈瘤と解剖を示した;これらの合併症はapoE-KOマウスでは観察されなかった.
結論:
- eNOS欠乏症は動脈硬化症を悪化させ,ネズミのモデルでは冠動脈疾患を誘発する.
- この研究は,第1回,心筋不全,心臓発作,心不全を伴う遠隔冠動脈硬化症のネズミモデルを提示しています.
- DKOマウスの心血管合併症は,高血圧と機能障害を含む,高血圧にのみ起因するものではありません.
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