title: Lysophosphatidic acid does not cause blood/lymphatic vessel plasticity in the rat mesentery culture model.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Sweat
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Azimi
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.
authors.forename: Ariana D
authors.initials: AD
authors.lastname: Suarez-Martinez
authors.affiliation: Department of Pharmacology, Tulane University, New Orleans, Louisiana.
authors.forename: Prasad
authors.initials: P
authors.lastname: Katakam
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana wmurfee@tulane.edu.
authors.forename: Walter L
authors.initials: WL
authors.lastname: Murfee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D000066670:Cell Plasticity / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D042583:Lymphangiogenesis / Q000187:drug effects; D042601:Lymphatic Vessels / Q000187:drug effects* / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D008246:Lysophospholipids; C533408:Lyve1 protein, rat; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C032881:lysophosphatidic acid
keywords: Angiogenesis; endothelial cell; lymphangiogenesis; lymphatic; lysophosphatidic acid; microcirculation