レジスティンは内皮細胞の活性化を促進する:アディポキンと内皮細胞の相互作用のさらなる証拠
Subodh Verma1, Shu-Hong Li, Chao-Hung Wang
1Division of Cardiac Surgery, Toronto General Hospital, 14EN-215, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4. subodh.verma@sympatico.ca
Circulation
|July 23, 2003
まとめ
脂肪細胞のホルモンであるレジスティンは,エンドセリン-1 (ET-1) の放出を増やし,ECを促進することによって,内皮細胞 (ECs) を直接活性化します.
科学分野:
- 内分泌学と新陳代謝について
- 心血管生物学 心血管生物学
- 分子生物学は分子生物学である.
背景:
- レジスティンなどのアディポサイト由来ホルモンは,インスリン抵抗性と心血管疾患の関連づけに関与しています.
- レジスティンは新しいアディポキンで,代謝および心血管疾患における潜在的な役割を持っています.
研究 の 目的:
- レジスティンの内皮活性化に対するレジスティンの直接的な影響を調査する.
- レジスティンが内皮細胞機能に影響を与える分子機構を解明する.
主な方法:
- ヒト再結合レジスティンは,内皮細胞 (ECs) を治療するために使用されました.
- 試験では,エンドセリン-1 (ET-1) 放出,ET-1 mRNA発現,および酸化窒素 (NO) 産生を測定した.
- 遺伝子リポーターは,AP-1サイト機能を含む,ET-1プロモーター活動に対するレジスティンの効果を評価した.
- 血管細胞粘着分子 (VCAM-1),単細胞化学誘導体ケモカイン (MCP-1),腫瘍死滅因子受容体関連因子-3 (TRAF3) の発現レベルが評価されました.
主要な成果:
- レジスティンは,NOの産生に影響を与えることなく,ECにおけるET-1放出とET-1mRNA発現を著しく増加させた.
- レジスティンは,AP-1転写因子結合部位に依存する,強化されたET-1プロモーター活性.
- TRAF3発現をダウンレギュレーションしながら,上調のVCAM-1とMCP-1発現に抵抗する.
- CD40リガンドによって誘発された抵抗性の強化されたMCP-1生成.
結論:
- レジスティンは,部分的にAP-1部位活性化によるET-1放出の増加を通じて,内皮細胞活性化を直接促進する.
- レジスティンは,炎症誘発性粘着分子とケモカイン (VCAM-1,MCP-1) を上調し,CD40信号伝達の阻害体であるTRAF3を下調する.
- これらの発見は,レジスティンがメカニズム的にメタボリックシンドロームにおける心血管疾患の発症に関連していることを示唆しています.
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