Aryal Bibek, Shimizu Toshiaki, Kadono Jun, Furoi Akira, Komokata Teruo, Inoue Maki, Ikeda Shunichiro, Fukukura Yoshihiko, Nakamura Masatoshi, Yamakuchi Munekazu, Hashiguchi Teruto, Imoto Yutaka
Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
PLoS One. 2016 Mar 1;11(3):e0150446. doi: 10.1371/journal.pone.0150446. eCollection 2016.
Liver regeneration (LR) involves an early inductive phase characterized by the proliferation of hepatocytes, and a delayed angiogenic phase distinguished by the expansion of non-parenchymal compartment. The interest in understanding the mechanism of LR has lately shifted from the proliferation and growth of parenchymal cells to vascular remodeling during LR. Angiogenesis accompanied by LR exerts a pivotal role to accomplish the process. Vascular endothelial growth factor (VEGF) has been elucidated as the most dynamic regulator of angiogenesis. From this perspective, platelet derived/Intra-platelet (IP) VEGF-A should be associated with LR.
Thirty-seven patients diagnosed with hepatocellular carcinoma and undergoing partial hepatectomy (PH) were enrolled in the study. Serum and IP VEGF-A was monitored preoperatively and at four weeks of PH. Liver volumetry was determined on computer models derived from computed tomography (CT) scan.
Serum and IP VEGF-A was significantly elevated at four weeks of PH. Preoperative IP VEGF-A was higher in patients with advanced cancer and vascular invasion. Postoperative IP VEGF-A was higher after major liver resection. There was a statistically significant correlation between postoperative IP VEGF-A and the future remnant liver volume. Moreover, the soluble vascular endothelial growth factor receptor-1 (sVEGFR1) was distinctly down-regulated suggesting a fine-tuned angiogenesis at the later phase of LR.
IP VEGF-A is overexpressed during later phase of LR suggesting its implications in inducing angiogenesis during LR.
肝再生(LR)包括一个以肝细胞增殖为特征的早期诱导阶段,以及一个以非实质区室扩张为特征的延迟血管生成阶段。最近,对理解肝再生机制的兴趣已从实质细胞的增殖和生长转向肝再生过程中的血管重塑。伴随肝再生的血管生成在完成这一过程中发挥着关键作用。血管内皮生长因子(VEGF)已被阐明是血管生成最活跃的调节因子。从这个角度来看,血小板衍生/血小板内(IP)VEGF-A应该与肝再生相关。
本研究纳入了37例诊断为肝细胞癌并接受部分肝切除术(PH)的患者。术前及肝切除术后四周监测血清和IP VEGF-A。通过计算机断层扫描(CT)扫描获得的计算机模型测定肝脏体积。
肝切除术后四周血清和IP VEGF-A显著升高。晚期癌症和血管侵犯患者术前IP VEGF-A较高。大肝切除术后术后IP VEGF-A较高。术后IP VEGF-A与未来残余肝脏体积之间存在统计学显著相关性。此外,可溶性血管内皮生长因子受体-1(sVEGFR1)明显下调,提示肝再生后期血管生成的精细调节。
IP VEGF-A在肝再生后期过度表达,提示其在肝再生过程中诱导血管生成的作用。