Sweat Richard S, Azimi Mohammad S, Suarez-Martinez Ariana D, Katakam Prasad, Murfee Walter L
Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.
Department of Pharmacology, Tulane University, New Orleans, Louisiana.
Physiol Rep. 2016 Jul;4(13). doi: 10.14814/phy2.12857.
Understanding the mechanisms behind endothelial cell identity is crucial for the goal of manipulating microvascular networks. Lysophosphatidic acid (LPA) and serum stimulation have been suggested to induce a lymphatic identity in blood endothelial cells in vitro. The objective of this study was to determine if LPA or serum induces blood-to-lymphatic vessel phenotypic transition in microvascular networks. The rat mesentery culture model was used to observe the effect of stimulation on blood and lymphatic microvascular networks ex vivo. Vascularized mesenteric tissues were harvested from adult Wistar rats and cultured with LPA or 10% serum for up to 5 days. Tissues were then immunolabeled with PECAM to identify blood vessels and LYVE-1 or Prox1 to identify lymphatic vessels. We show that while LPA caused capillary sprouting and increased vascular length density in adult microvascular networks, LPA did not cause a blood-to-lymphatic phenotypic transition. The results suggest that LPA is not sufficient to cause blood endothelial cells to adopt a lymphatic identity in adult microvascular networks. Similarly, serum stimulation caused robust angiogenesis and increased lymphatic/blood vessel connections, yet did not induce a blood-to-lymphatic phenotypic transition. Our study highlights an understudied area of lymphatic research and warrants future investigation into the mechanisms responsible for the maintenance of blood and lymphatic vessel identity.
了解内皮细胞特性背后的机制对于操控微血管网络这一目标至关重要。溶血磷脂酸（LPA）和血清刺激已被认为可在体外诱导血液内皮细胞形成淋巴管特性。本研究的目的是确定LPA或血清是否会在微血管网络中诱导血液血管向淋巴管的表型转变。大鼠肠系膜培养模型用于在体外观察刺激对血液和淋巴管微血管网络的影响。从成年Wistar大鼠获取血管化的肠系膜组织，并用LPA或10%血清培养长达5天。然后用PECAM进行免疫标记以识别血管，用LYVE-1或Prox1识别淋巴管。我们发现，虽然LPA在成年微血管网络中引起毛细血管芽生并增加血管长度密度，但LPA并未导致血液血管向淋巴管的表型转变。结果表明，在成年微血管网络中，LPA不足以使血液内皮细胞获得淋巴管特性。同样，血清刺激引起强烈的血管生成并增加淋巴管/血管连接，但并未诱导血液血管向淋巴管的表型转变。我们的研究突出了淋巴管研究中一个尚未充分研究的领域，值得未来对负责维持血液和淋巴管特性的机制进行研究。
