Kim Hyun Kyung, Song Kyung Soon, Chung Jun-Ho, Lee Kyoung Rhan, Lee Se-Na
Hematologic Malignancies Branch, Division of Special Cancers, Research Institute & Hospital, National Cancer Centre, 809 Madu, Ilsan, Goyang, Gyeonggi 411-769, Republic of Korea.
Br J Haematol. 2004 Feb;124(3):376-84. doi: 10.1046/j.1365-2141.2003.04773.x.
Platelet microparticles (PMP) are endogenous substances generated during the coagulation process in a hypercoagulable state. This study demonstrated that PMP promote the proliferation and survival, migration, and tube formation in human umbilical vein endothelial cells (HUVEC). Heat-treated PMP did not significantly decrease the angiogenic activity in HUVEC compared with that of the untreated PMP. Meanwhile when PMP were treated with activated charcoal, a procedure known to remove the lipid growth factors, the angiogenic activity was significantly reduced. These results suggest that the lipid component(s) of the PMP may be major active factor(s) and that protein component(s) may be minor contributor(s). PMP were also shown to augment endothelial progenitor cell differentiation in peripheral blood mononuclear cells. In addition, PMP-stimulated proliferation, chemotaxis and tube formation of the HUVEC was mediated via the Pertussis toxin-sensitive G protein, extracellular signal-regulated kinase and the phosphoinositide 3-kinase pathway. Herein, a new action of PMP was demonstrated to be a potent angiogenic stimulator. It is expected that in pathological states such as a growing tumour, PMP shed from the circulating platelets may reach adequate concentrations and that the elevated levels of PMP could contribute to florid formation of new blood vessels.
血小板微粒(PMP)是在高凝状态下凝血过程中产生的内源性物质。本研究表明,PMP可促进人脐静脉内皮细胞(HUVEC)的增殖、存活、迁移和管腔形成。与未处理的PMP相比,热处理的PMP并未显著降低HUVEC中的血管生成活性。同时,当用活性炭处理PMP时(这是一种已知可去除脂质生长因子的方法),血管生成活性显著降低。这些结果表明,PMP的脂质成分可能是主要活性因子,而蛋白质成分可能是次要贡献因子。PMP还被证明可增强外周血单核细胞中内皮祖细胞的分化。此外,PMP刺激的HUVEC增殖、趋化性和管腔形成是通过百日咳毒素敏感的G蛋白、细胞外信号调节激酶和磷酸肌醇3激酶途径介导的。在此,PMP的一种新作用被证明是一种有效的血管生成刺激剂。预计在诸如肿瘤生长等病理状态下,循环血小板释放的PMP可能达到足够的浓度,且PMP水平的升高可能有助于新血管的旺盛形成。