Bioelectric impact of pathological angiogenesis on vascular function
Bioelectric impact of pathological angiogenesis on vascular function
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DOI：
10.1073/pnas.1604757113
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发表时间：
2016-08-30
影响因子：
11.1
通讯作者：
Padovani-Claudio, Dolly A.
中科院分区：
文献类型：
--
作者：
Puro, Donald G.;Kohmoto, Ryohsuke;Padovani-Claudio, Dolly A.
尽管有新的分子疗法，病理性血管生成（如许多炎症、免疫、恶性和缺血性疾病中所见）仍然是巨大的健康负担。进一步的治疗进展可能需要更好地了解新生血管病理生理学。令人惊讶的是，尽管众所周知跨膜电压可以调节血管功能，但以前没有报道过病理性血管生成的生物电分析。使用穿孔贴片技术测量人类视网膜新生血管标本和啮齿动物视网膜新生血管模型中的血管电压，我们发现病理性新生血管会产生极高的电压。电生理学实验表明，来自异常位置的视网膜前新生血管复合体的电压被传输到视网膜内血管网络中。随着广泛的新生血管形成，这种电压输入很大，并将视网膜内血管的膜电位提高到超超极化水平。与这种超超极化同时发生的是，血管舒缩对缺氧的反应也发生了根本性的改变。与正常视网膜中观察到的代偿性扩张不同，小动脉因缺氧而收缩。这种异常的血管收缩会加剧缺氧，这提出了一种可能性：新生血管形成对血管功能的生物电影响是一种以前未被认识到的维持缺氧驱动的血管生成的病理生理机制。
Pathological angiogenesis, as seen in many inflammatory, immune, malignant, and ischemic disorders, remains an immense health burden despite new molecular therapies. It is likely that further therapeutic progress requires a better understanding of neovascular pathophysiology. Surprisingly, even though transmembrane voltage is well known to regulate vascular function, no previous bioelectric analysis of pathological angiogenesis has been reported. Using the perforated-patch technique to measure vascular voltages in human retinal neovascular specimens and rodent models of retinal neovascularization, we discovered that pathological neovessels generate extraordinarily high voltage. Electrophysiological experiments demonstrated that voltage from aberrantly located preretinal neovascular complexes is transmitted into the intraretinal vascular network. With extensive neovascularization, this voltage input is substantial and boosts the membrane potential of intraretinal blood vessels to a suprahyperpolarized level. Coincident with this suprahyperpolarization, the vasomotor response to hypoxia is fundamentally altered. Instead of the compensatory dilation observed in the normal retina, arterioles constrict in response to an oxygen deficiency. This anomalous vasoconstriction, which would potentiate hypoxia, raises the possibility that the bioelectric impact of neovascularization on vascular function is a previously unappreciated pathophysiological mechanism to sustain hypoxia-driven angiogenesis.