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首页> 外文期刊>Cell cycle >PDGF/VEGF system activation and angiogenesis following initial post ovariectomy meningeal microvessel loss.
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PDGF/VEGF system activation and angiogenesis following initial post ovariectomy meningeal microvessel loss.

机译：卵巢切除术后最初的脑膜微血管丢失后，PDGF / VEGF系统激活和血管生成。

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Recently we demonstrated that cessation of ovarian hormone production causes dramatic vascular remodeling in meningeal microvascular networks characterized by a significant microvessel loss. Further, even two months post ovariectomy (OVX), dura mater microvessels remain destabilized due to a decline in estrogen-mediated angiopoietin-1 (Ang-1) expression and Ang-1/Tie-2 signaling. Such destabilized microvessels could be susceptible to either further regression or angiogenesis. In this study, we tested the hypothesis that initial estrogen-dependent loss of meningeal microvessels following OVX triggers stromal and vascular hypoxic responses aiming at restoring dura microvasculature. We demonstrate that two months post OVX, there is an activation of the hypoxia-inducible factor-1alpha (HIF-1alpha) and PDGF/VEGF system in the dura mater stroma and microvasculature of experimental animals accompanied by a shift in the balance between PI3K and PLCgamma activity downstream of PDGF/VEGF signaling toward PI3K. It appears that the latter serves as a molecular switch favoring angiogenic responses rather than further regression of destabilized microvessels. Indeed, consistent with this idea, we have found a considerable angiogenic activity in meningeal microvascular networks that previously underwent regression. These results indicate that angioadaptation of meningeal microvessels in response to cessation of ovarian hormone production is not a unidirectional, but a very complex multi-stage process regulated on many levels. The implication of this study is that therapeutic interventions, including estrogen-based hormone replacement therapy, with physiological angioadaptation in postmenopausal or post OVX women need to be approached with the extreme caution.
机译：最近，我们证明，停止卵巢激素的产生会导致脑膜微血管网络中明显的微血管丢失，从而引起剧烈的血管重塑。此外，即使在卵巢切除术（OVX）的两个月后，由于雌激素介导的血管生成素1（Ang-1）表达和Ang-1 / Tie-2信号的减少，硬脑膜微血管仍然不稳定。这种不稳定的微血管可能易于进一步消退或血管生成。在这项研究中，我们测试了以下假设：OVX后脑膜微血管的初始雌激素依赖性损失会触发旨在恢复硬脑膜微血管的基质和血管缺氧反应。我们证明，OVX后两个月，实验动物的硬脑膜基质和微脉管系统中存在缺氧诱导因子1α（HIF-1alpha）和PDGF / VEGF系统的激活，并伴随着PI3K和PDGF / VEGF向PI3K传递信号时下游的PLCgamma活性。似乎后者充当促进血管生成反应的分子开关，而不是不稳定的微血管的进一步消退。的确，与这个想法一致，我们已经发现了先前经历消退的脑膜微血管网络中相当大的血管生成活性。这些结果表明，响应于停止卵巢激素产生，脑膜微血管的血管适应不是单向的，而是在许多水平上调节的非常复杂的多阶段过程。这项研究的意义在于，在绝经后或OVX后妇女中应采取包括生理性血管适应在内的治疗干预措施，包括基于雌激素的激素替代疗法。

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