Laboratory of Neuroscience, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
Cells. 2022 Sep 3;11(17):2755. doi: 10.3390/cells11172755.
Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that leptin potentiates angiogenesis and plays a beneficial role in stroke. However, the proangiogenic effect of leptin on ICH has not been adequately explored. Moreover, leptin triggers post-ICH angiogenesis through pericyte, an important component of forming new blood vessels, which remains unclear. Here, we reported that exogenous leptin infusion dose-dependent promoted vascular endothelial cells survival and proliferation at chronic stage of ICH mice. Additionally, leptin robustly ameliorated pericytes loss, enhanced pericytes proliferation and migration in ICH mice in vivo, and in ICH human brain microvascular pericytes (HBVPC) in vitro. Notably, we showed that pericytes-derived pro-angiogenic factors were responsible for enhancing the survival, proliferation and tube formation followed leptin treatment in human brain microvascular endothelial cells (HCMEC/D3)/HBVPC co-culture models. Importantly, considerable improvements in neurobehavioral function and hostile microenvironment were observed in leptin treatment ICH mice, indicating that better vascular functionality post ICH improves outcome. Mechanistically, this study unveiled that leptin boost post-ICH angiogenesis potentially through modulation of leptin receptor (leptinR)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in pericyte. Thus, leptin may be a lucrative option for the treatment of ICH.
血管生成是脑出血（ICH）后神经恢复的重要内源性脑自我修复过程。越来越多的证据表明，瘦素促进血管生成，并在中风中发挥有益作用。然而，瘦素对 ICH 的促血管生成作用尚未得到充分探索。此外，瘦素通过周细胞触发 ICH 后的血管生成，周细胞是形成新血管的重要组成部分，其作用机制尚不清楚。在这里，我们报道了外源性瘦素输注在 ICH 小鼠慢性期呈剂量依赖性促进血管内皮细胞的存活和增殖。此外，瘦素在体内显著改善了 ICH 小鼠的周细胞丢失，增强了其增殖和迁移，在体外也增强了 ICH 人脑微血管周细胞（HBVPC）的增殖和迁移。值得注意的是，我们表明周细胞衍生的促血管生成因子是瘦素处理后在人脑血管内皮细胞（HCMEC/D3）/HBVPC 共培养模型中增强细胞存活、增殖和管状形成的原因。重要的是，在接受瘦素治疗的 ICH 小鼠中观察到神经行为功能和恶劣微环境得到了相当大的改善，这表明 ICH 后更好的血管功能可改善预后。从机制上讲，这项研究揭示了瘦素通过调节周细胞中的瘦素受体（leptinR）/信号转导和转录激活因子 3（STAT3）信号通路来促进 ICH 后的血管生成。因此，瘦素可能是治疗 ICH 的一种有前途的选择。
