CAJ | 학술논문

目的：探讨血管紧张素II（Ang II）1型受体相关蛋白（ATRAP）通过Ang II 1型受体（AT1R）调节血管平滑肌细胞（VSMCs）增殖及血管内膜增生的作用机制。方法将ATRAP cDNA转至pcDNA3载体，然后转染至来源于成年SD大鼠胸主动脉的VSMCs。VSMCs 内DNA合成，细胞外信号调控激酶（ERK）及ERK磷酸化的表达分别通过3H胸腺嘧啶核苷的合成和Western blot方法检测。利用球囊损伤血管的模型，观察转染和未转染ATRAP cDNA的12周雄性SD大鼠的血管形态学变化。结果在Ang II刺激VSMCs 48h后，ATRAP过表达可以抑制Ang II诱导的3H胸腺嘧啶核苷的合成（P<0.05）。在VSMCs内，Ang II的刺激增加了ERK的磷酸化，大约60min达到峰值。ATRAP的过表达使磷酸化ERK的活性显著降低（P<0.05），并明显抑制了损伤动脉的新生内膜增生。结论 AT1受体介导的ERK活性在Ang II调节的VSMCs增殖中起重要作用。ATRAP对VSMCs增殖和新生内膜形成的抑制作用可能是由于其干扰AT1受体介导的ERK活性。目的探讨血管紧张素II（Ang II）1型受体相关蛋白（ATRAP）通过Ang II 1型受体（AT1R）调节血管平滑肌细胞（VSMCs）增殖及血管内膜增生的作用机制。方法将ATRAP cDNA转至pcDNA3载体，然后转染至来源于成年SD大鼠胸主动脉的VSMCs。VSMCs 内DNA合成，细胞外信号调控激酶（ERK）及ERK磷酸化的表达分别通过3H胸腺嘧啶核苷的合成和Western blot方法检测。利用球囊损伤血管的模型，观察转染和未转染ATRAP cDNA的12周雄性SD大鼠的血管形态学变化。结果在Ang II刺激VSMCs 48h后，ATRAP过表达可以抑制Ang II诱导的3H胸腺嘧啶核苷的合成（P<0.05）。在VSMCs内，Ang II的刺激增加了ERK的磷酸化，大约60min达到峰值。ATRAP的过表达使磷酸化ERK的活性显著降低（P<0.05），并明显抑制了损伤动脉的新生内膜增生。结论 AT1受体介导的ERK活性在Ang II调节的VSMCs增殖中起重要作用。ATRAP对VSMCs增殖和新生内膜形成的抑制作用可能是由于其干扰AT1受体介导的ERK活性。目的：探討血管緊張素II（Ang II）1型受體相關蛋白（ATRAP）通過Ang II 1型受體（AT1R）調節血管平滑肌細胞（VSMCs）增殖及血管內膜增生的作用機製。方法將ATRAP cDNA轉至pcDNA3載體，然後轉染至來源于成年SD大鼠胸主動脈的VSMCs。VSMCs 內DNA閤成，細胞外信號調控激酶（ERK）及ERK燐痠化的錶達分彆通過3H胸腺嘧啶覈苷的閤成和Western blot方法檢測。利用毬囊損傷血管的模型，觀察轉染和未轉染ATRAP cDNA的12週雄性SD大鼠的血管形態學變化。結果在Ang II刺激VSMCs 48h後，ATRAP過錶達可以抑製Ang II誘導的3H胸腺嘧啶覈苷的閤成（P<0.05）。在VSMCs內，Ang II的刺激增加瞭ERK的燐痠化，大約60min達到峰值。ATRAP的過錶達使燐痠化ERK的活性顯著降低（P<0.05），併明顯抑製瞭損傷動脈的新生內膜增生。結論 AT1受體介導的ERK活性在Ang II調節的VSMCs增殖中起重要作用。ATRAP對VSMCs增殖和新生內膜形成的抑製作用可能是由于其榦擾AT1受體介導的ERK活性。目的探討血管緊張素II（Ang II）1型受體相關蛋白（ATRAP）通過Ang II 1型受體（AT1R）調節血管平滑肌細胞（VSMCs）增殖及血管內膜增生的作用機製。方法將ATRAP cDNA轉至pcDNA3載體，然後轉染至來源于成年SD大鼠胸主動脈的VSMCs。VSMCs 內DNA閤成，細胞外信號調控激酶（ERK）及ERK燐痠化的錶達分彆通過3H胸腺嘧啶覈苷的閤成和Western blot方法檢測。利用毬囊損傷血管的模型，觀察轉染和未轉染ATRAP cDNA的12週雄性SD大鼠的血管形態學變化。結果在Ang II刺激VSMCs 48h後，ATRAP過錶達可以抑製Ang II誘導的3H胸腺嘧啶覈苷的閤成（P<0.05）。在VSMCs內，Ang II的刺激增加瞭ERK的燐痠化，大約60min達到峰值。ATRAP的過錶達使燐痠化ERK的活性顯著降低（P<0.05），併明顯抑製瞭損傷動脈的新生內膜增生。結論 AT1受體介導的ERK活性在Ang II調節的VSMCs增殖中起重要作用。ATRAP對VSMCs增殖和新生內膜形成的抑製作用可能是由于其榦擾AT1受體介導的ERK活性。
목적：탐토혈관긴장소II（Ang II）1형수체상관단백（ATRAP）통과Ang II 1형수체（AT1R）조절혈관평활기세포（VSMCs）증식급혈관내막증생적작용궤제。방법장ATRAP cDNA전지pcDNA3재체，연후전염지래원우성년SD대서흉주동맥적VSMCs。VSMCs 내DNA합성，세포외신호조공격매（ERK）급ERK린산화적표체분별통과3H흉선밀정핵감적합성화Western blot방법검측。이용구낭손상혈관적모형，관찰전염화미전염ATRAP cDNA적12주웅성SD대서적혈관형태학변화。결과재Ang II자격VSMCs 48h후，ATRAP과표체가이억제Ang II유도적3H흉선밀정핵감적합성（P<0.05）。재VSMCs내，Ang II적자격증가료ERK적린산화，대약60min체도봉치。ATRAP적과표체사린산화ERK적활성현저강저（P<0.05），병명현억제료손상동맥적신생내막증생。결론 AT1수체개도적ERK활성재Ang II조절적VSMCs증식중기중요작용。ATRAP대VSMCs증식화신생내막형성적억제작용가능시유우기간우AT1수체개도적ERK활성。목적탐토혈관긴장소II（Ang II）1형수체상관단백（ATRAP）통과Ang II 1형수체（AT1R）조절혈관평활기세포（VSMCs）증식급혈관내막증생적작용궤제。방법장ATRAP cDNA전지pcDNA3재체，연후전염지래원우성년SD대서흉주동맥적VSMCs。VSMCs 내DNA합성，세포외신호조공격매（ERK）급ERK린산화적표체분별통과3H흉선밀정핵감적합성화Western blot방법검측。이용구낭손상혈관적모형，관찰전염화미전염ATRAP cDNA적12주웅성SD대서적혈관형태학변화。결과재Ang II자격VSMCs 48h후，ATRAP과표체가이억제Ang II유도적3H흉선밀정핵감적합성（P<0.05）。재VSMCs내，Ang II적자격증가료ERK적린산화，대약60min체도봉치。ATRAP적과표체사린산화ERK적활성현저강저（P<0.05），병명현억제료손상동맥적신생내막증생。결론 AT1수체개도적ERK활성재Ang II조절적VSMCs증식중기중요작용。ATRAP대VSMCs증식화신생내막형성적억제작용가능시유우기간우AT1수체개도적ERK활성。
Objective To investigate the effect of angiotensin II (Ang II) type 1 (AT1) receptor-associated protein (ATRAP) on vascular smooth muscle cells (VSMCs) proliferation and neointimal formation mediated by AT1 receptor. Methods ATRAP cDNA was subcloned into pcDNA3 vector, and was transfected into VSMCs, which were isolated from thoracic aorta of adult Sprague-Dawley (SD) rats. DNA synthesis, extracellular signal-regulated kinase (ERK) and phospho-ERK expression in VSMCs were analyzed by measurement of 3H thymidine synthesis and Western blot respectively. Morphological changes were observed in the balloon injured artery of 12-week male SD rats with or without transfection of ATRAP cDNA. Results ATRAP overexpression in VSMCs inhibited Ang II-induced 3H thymidine synthesis after 48 h stimulation (P<0.05). In VSMCs, Ang II stimulation increased the phosphorylation of ERK, which reached the peak at 60min. ATRAP overexpression in injuried arteries significantly decreased the activation of phospho-ERK and inhibited neointimal formation (P<0.05). Conclusion The AT1 receptor-mediated activation of ERK plays an essential role in Ang II-regulated VSMCs proliferation. The inhibitory effects of ATRAP on VSMCs proliferation and neointimal formation might be due to interfering with AT1 receptor-mediated activation of ERK.