Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis

Laura Carramolino, Joana Fuentes, Clara García-Andrés, Valeria Azcoitia, Dieter Riethmacher, Miguel Torres

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

RATIONALE: Several mutations that impair the development of blood lineages in the mouse also impair the formation of the lymphatic vasculature and its separation from the blood vasculature. However, the basis for these defects has remained unknown because the mutations characterized affect more than one blood lineage. OBJECTIVE: We tested the hypothesis that megakaryocytes/platelets are required for the formation of the lymphatic vasculature and its separation from the blood vascular system. METHODS AND RESULTS: We characterized the vascular patterning defects of mice deficient for the homeodomain transcription factor Meis1 (myeloid ecotropic viral integration site 1), which completely lack megakaryocyte/platelets. Meis1 null embryos fail to separate the blood and lymphatic vasculature, showing blood-filled primary lymphatic sacs and superficial lymphatic vessels. To test the involvement of megakaryocytes/ platelets in this phenotype, we generated megakaryocyte/platelet-specific deficient mice by targeted lineage ablation, without affecting other blood lineages. This model reproduces the lymphatic/blood vasculature separation defects observed in Meis1 mutants. A similar phenotype was induced by antibody-mediated ablation of circulating platelets in wild type mice. Strong association of platelets with vascular endothelium at regions of contact between lymphatic sacs and veins confirmed a direct role of platelets in the separation of the 2 vasculatures. CONCLUSIONS: In addition to their known protective function in the response accidental vascular injury, platelets are also required during embryonic lymphangiogenesis for the separation of the nascent lymphatic vasculature from blood vessels.

Original languageEnglish
Pages (from-to)1197-1201
Number of pages5
JournalCirculation Research
Volume106
Issue number7
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

Fingerprint

Blood Platelets
Megakaryocytes
Virus Integration
Blood Vessels
Lymphangiogenesis
Phenotype
Mutation
Lymphatic Vessels
Vascular System Injuries
Vascular Endothelium
Veins
Transcription Factors
Embryonic Structures
Antibodies

Keywords

  • Angiogenesis
  • Lymphangiogenesis
  • Lymphatics
  • Megakaryocytes
  • Meis1
  • Platelets

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis. / Carramolino, Laura; Fuentes, Joana; García-Andrés, Clara; Azcoitia, Valeria; Riethmacher, Dieter; Torres, Miguel.

In: Circulation Research, Vol. 106, No. 7, 04.2010, p. 1197-1201.

Research output: Contribution to journalArticle

Carramolino, Laura ; Fuentes, Joana ; García-Andrés, Clara ; Azcoitia, Valeria ; Riethmacher, Dieter ; Torres, Miguel. / Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis. In: Circulation Research. 2010 ; Vol. 106, No. 7. pp. 1197-1201.
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