11, 12－環氧二十碳三烯酸促進人類血管內皮前驅幹細胞血管再生作用

11, 12－環氧二十碳三烯酸是藉由人類細胞色素P450環氧酶（CYP2J2）的作用，將花生四烯酸轉換而來，其具有影響心血管功能的作用。而人類血管內皮前驅幹細胞被視為血管內皮細胞的先驅者，透過血管再生作用，具有預防缺血性傷害的功能。然而11, 12－環氧二十碳三烯酸作用在血管內皮前驅幹細胞所誘發血管再生的分子機制仍未明。本研究主要透過血管形成方法、西方點墨法，探討11, 12－環氧二十碳三烯酸是否可以調節血管再生作用，結果顯示11, 12－環氧二十碳三烯酸可以隨著濃度增加（3, 30, 50 nM）促進血管再生作用，其分子機制主要是11, 12－環氧二十碳三烯酸透過增強Akt及eNOS蛋白磷酸化，同時藉由抑制細胞周期蛋白p21^(Cip1)的表現及增加cyclin D1及E2F1表現，促進人類血管內皮前驅幹細胞血管再生作用。本研究成果未來或許可以進一步被應用到臨床營養預防用途上，藉由飲食影響11, 12－環氧二十碳三烯酸的表現，以達到增加血管內皮前驅幹細胞活性、促進血管再生作用及減少罹患心血管疾病機率。

關鍵字

11, 12－環氧二十碳三烯酸；血管再生作用；人類血管內皮前驅幹細胞

並列摘要

11, 12-Epoxyeicosatrienoic acid (11, 12-EET) is synthesized from arachidonic acid (AA) by cytochrome P450 2J2 (CYP 2J2) epoxygenase and functions as an effector of cardiovascular function. Human endothelial progenitor cells (EPCs), a cell source for endothelial cells (ECs), play a crucial role in preventing ischemic injuries through postnatal neovasculogenesis. However, the molecular actions of 11, 12-EET on EPC-mediated neovasculogenesis have not yet been demonstrated. In the current study, we examined whether 11, 12-EET modulates neovasculogenesis processes using vascular tube formation and Western blot assays. Results suggested that 11, 12-EET (at concentrations of 3, 30, and 50 nM) dose-dependently induced neovasculogenesis. The major mechanism was through phosphorylation (i.e., activation) of Akt and endothelial-nitric oxide synthase (eNOS) proteins, suppression of p21^(cip1) cell cycle inhibitor protein, and upregulation of cyclin D1 and E2F1 proteins in human EPCs. These results may be applicable to future prevention studies in clinical trials. They also suggest that diet-mediated upregulation of 11, 12-EET may augment the function of EPCs and neovasculogenesis, and prevent cardiovascular diseases.

並列關鍵字

11, 12-epoxyeieosatrienoie acid ； neovasculogenesis ； Akt ； eNOS ； cyclin D1 ； human endothelial progenitor cells

國際替代計量

11, 12－環氧二十碳三烯酸促進人類血管內皮前驅幹細胞血管再生作用

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