ADP에 의해서 활성화된 혈관평활근 세포의 증식에 관여하는 Integrin의 종류와 신호 전달 경로

Background : Adenosine diphosphate (ADP),which is usually secreted from activated platelets, activates integrin arb3, arb5, and a5b1 on human vascular smooth muscle cells. Integrins have an important role in the proliferation of vascular smooth muscle cells. ADP may stimulate the proliferation of vascular smooth muscle cells by the activation of integrins. Integrins mediating ADP=stimulated proliferation of vascular smooth muscle cells and signal transduction pathway of ADP stimulation were investigated in this study. Methods : MIT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) assay was used to evaluate ADP or ATP-stimulated proliferation of human aortic smooth muscle cells (HASMC). In some experiments, HASMC were incubated with U73122, an inhibitor of phospholipase C, or monoclonal antibodies (mAb) to integrins after ADP or ATP stimulation. Results : ADP and ATP increased the proliferation of HASMC in a dose-dependent manner. U73122 inhibited ADP- or ATP- stimulated proliferation of HASMC. ADP-stimulated proliferation of HASMC was inhibited either by c7E3, a blocking mAb to integrin b3 or by LM609, a blocking mAb to integrin arb3 (37% and 26% inhibition, respectively; p