臓の胆汁塩依存リパゼは,滑らかな筋肉細胞の増殖を誘発する
Nathalie Augé1, Ouafa Rebaï, Josette Lepetit-Thévenin
1INSERM U-466, Marseille, France.
Circulation
|June 25, 2003
まとめ
胆汁塩依存リパゼ (BSDL) は,動脈硬化症における滑らかな筋肉細胞 (SMC) の増殖を促進する. 動脈の病変に含まれるこの酵素は,重要な細胞経路を活性化することによって,疾患の発症を促す可能性があります.
科学分野:
- 心血管生物学 心血管生物学
- 酵素学 酵素学とは
- セルラー・シグナリング
背景:
- 胆汁塩依存リパゼ (BSDL) は,臓のアシナ細胞によって分泌され,LDLに関連した循環血液に含まれています.
- BSDLは,動脈硬化性病変における滑らかな筋肉細胞 (SMC) にも局所化します.
- SMCにおけるBSDLの役割とその動脈硬化への貢献は十分に理解されていません.
研究 の 目的:
- BSDLがSMCに及ぼす影響を調査する.
- 動脈硬化症の文脈でBSDLがSMCの増殖に影響を与えているかどうかを判断する.
主な方法:
- 猿とヒトの動脈硬化病変におけるBSDL発現を検出するための免疫ヒストキミストリー.
- 培養SMCを用いたインビトロ研究で,BSDLのミトゲン性を評価した.
- ERK1/2を含むシグナル伝達経路と媒介者生産 (ディアシルグリセロール,オイル酸,FGF2) の分析.
主要な成果:
- BSDL発現は動脈硬化性病変で検出され,SMCと関連していますが,マクロファージではありません.
- BSDLは,培養SMCに有意なミトゲン活性を示し,ヘパリンと抗BSDL抗体によって抑制された.
- BSDLが誘発した増殖は,ERK1/2経路の活性化とFGF2の放出,ダイアシルグリセロールとオイル酸の産生を伴う.
結論:
- 循環するBSDLは動脈内側に存在し,SMCと関連しています.
- BSDLは,SMCの増殖を促進し,動脈硬化性病変の発生に寄与する可能性があります.
- BSDLをターゲットにすることは,動脈硬化症の潜在的な治療戦略である可能性があります.
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