2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38801Epidemiological studies have shown that cigarette smoking is a major cause of atherosclerosis. Oxidants as well as nicotine in cigarette smoke have been implicated in atherogenesis. Cell adhesion molecules are closely related to the atherosclerogenesis, specially the ICAM-1, VCAM-1 and E-selectin up-regulation involved in the pathological procedure in the formation of atherosclerosis. Therefore, the down-regulation of cell adhesion molecules might become a method in preventing atherosclerosis. This research had previously discovered that the cigarette smoke extract (CSE) clearly caused the up-regulation of ICAM-1 and E-selectin in HUVEC. And the signal that induces ICAM-1 up-regulation in HUVEC is closely related to the actin cytoskeleton reorganization and activation of AP-1, instead of the ERK and JNK phosphorylation that caused by CSE in HUVEC. To understand further how CSE, through the reorganization of actin cytoskeleton, induces MAPK-independent pathway activating AP-1 that causes ICAM-1 up-regulation in HUVEC and develop its prevention, this project will discuss the following three topics in three years: (1) How CSE causes the reorganization of actin cytoskeleton and regulates the ICAM-1 expression. (2) The role of Jab1 (Jun activating binding protein), a co-activator of AP-1, in CSE induces the increase of ICAM-1 expression. (3) The prevention of CSE induces the up-regulation of ICAM-1 expression. The accomplishment of this project will be able to establish the following pathway: [CSE or nicotine􀃆 integrin, EGFR, ET-AR 􀃆 Rho family GTPase 􀃆 cytoskeleton reorganization 􀃆 Jab1 activation/nucleus trasnlocation 􀃆 c-Jun phosphorylation /AP-1 activation] involve in CSE-induced upregulation of ICAM-1 in HUVEC. Simultaneously, these results also help to know the inhibition and mechanism of stains, natural polyphenols (resveratrol, ECGC, quercetin) and tea extract (green tea, red tea and Pu-er tea) on the CSE-induced up-regulation of ICAM-1in HUVEC. The overall conclusion will approach to the basic theory and prevention to cardiovascular disease caused by cigarette smoking and provides new and valuable information for application. skeleton; Jab1; AP-1; Statin; Polyphenol; siRNA流病學的研究證實香煙是造成動脈硬化症(atherosclerosis)主要的原因。細胞黏著 分子(cell adhesion molecule)與動脈硬化症關係密切，尤其是细胞間黏著分子 -1(ICAM-1)、血管細胞黏著分子-1(VCAM-1)與E-選擇素(E-selectin)等參與動脈硬 化症形成的病理過程，且其基因多態性是動脈硬化症發生的危險因子。因此，針 對細胞黏著分子的抗黏著調節，將可能成為動脈硬化症有效的防治手段。本實驗 室先前的研究發現，香煙萃物(cigarette smoke extract/CSE)明顯造成人類臍靜脈內 皮細胞(HUVEC) ICAM-1 及E-selectin 蛋白質表現的增加，而誘發這個現象的訊號 傳遞與細胞微絲骨架(actin cytoskeleton)的重組(reorganization)及AP-1 轉錄因子的 活化有密切關係，與CSE 在HUVEC 造成的ERK 及JNK 活化磷酸化途徑則無關。 為進一步了解CSE 如何透過細胞骨架重組，引發MAPK-非依賴途徑，活化AP-1 轉錄活性，造成ICAM-1 表現增加詳細的控制途徑，並且研發其防治之道，本研 究計畫將以三年時間，探討下列三大議題：(1)香煙萃物如何造成細胞骨架重編並 調節ICAM-1 表現，(2) 探討Jab1(a co-activator of AP-1)在香煙萃物誘發ICAM-1 表現增加所扮演的角色，(3) 探討天然植物多酚、茶萃物對香煙萃物誘發ICAM-1 表現增加的防治效果及作用機制。本計畫的完成將可建立下列途徑 [香煙萃物/ 尼古丁􀃆 細胞受體(β-integrin, EGFR, ET-AR)􀃆 Rho family GTPase 􀃆 微絲細胞骨 架/微管細胞骨架重組 􀃆 Jab1 活化/細胞核轉移 􀃆 c-Jun 磷酸化/AP-1 轉錄活 化]，在CSE 誘發ICAM-1 在HUVEC 細胞表現增加所扮演的角色，同時也可了解 史他汀類藥劑(stain)、天然多酚[白藜蘆醇(resveratrol、綠茶多酚(ECGC)、槲黃素 (quercetin)及茶(綠茶、紅茶、普洱茶)浸出液，對CSE 誘發HUVEC 細胞ICAM-1 表現增加的抑制活性及機制，整體成果對香煙造成心血管疾病之基本學理及其防 治，可提供新穎且有應用價值之資訊。Project