Cardiovascular System - Lymphatic Development

Introduction

An important part of the cardiovascular system is the lymphatic vasculature, which functions to return interstitial fluid (lymph) to the bloodstream.

This system was first identified by Aselli G. 1627 in a paper "De Lacteibus sive Lacteis Venis", Quarto Vasorum Mesarai corum Genere novo invento. Milan: Mediolani

Some Recent Findings

The lymphatic vasculature: recent progress and paradigms. Oliver G, Alitalo K. Annu Rev Cell Dev Biol. 2005;21:457-83. Review. PMID: 16212503

"The field of lymphatic research has been recently invigorated by the identification of genes and mechanisms that control various aspects of lymphatic development. We are beginning to understand how, starting from a subgroup of embryonic venous endothelial cells, the whole lymphatic system forms in a stepwise manner. The generation of genetically engineered mice with defects in different steps of the lymphangiogenic program has provided models that are increasing our understanding of the lymphatic system in health and disease."

Lymphatic Vessels

Lymph capillaries
Lymph collecting vessels
Lymph ducts

Lymphatic Vessel Contraction

Lymphatic vessels undergo spontaneous rhythmic contractions which aid lymph flow. This is most easily demonstrated in models based upon mesentry lymphatics of the gastrointestinal tract. Contractile activity is regulated by physical factors (transmural pressure) and neurological (alpha-adrenergic, histamine, bradykinin) acting on lymphatic smooth muscle. Contractility and receptor expression may also be different in different parts of the lymphatic system.

Alpha-adrenergic - alpha 1- and not alpha 2-adrenoceptors.

Histamine - lymphatic smooth muscle via stimulation of H(1) (and in some vessels H(2)) receptors.

Bradykinin - chronotropic but not inotropic effects on lymphatic pump activity via stimulation of B1 receptors.

Molecular Development

Angiopoietins (Ang1–Ang4)

Notch probably mediates choice of fate between arterial and venous.

Prox1 Prospero-related Homeobox 1 - expressed in a subpopulation of blood endothelial cells that then generate, by both budding and sprouting, cells of the lymphatic vascular system. (OMIM - PROSPERO-RELATED HOMEOBOX 1; PROX1)

Tie (Tie1 and Tie2) tyrosine kinase receptors.

Vascular endothelial growth factor (VEGF) family of proteins and angiopoietin/Tie, Notch, and ephrin/Eph pathways play major roles in eary vessel development.

Abnormalities

Lymphangioma - dysplasia of childhood form lymphatic capillaries or collectors, which form fluid-filled cysts.

lymphatic spaces lined by endothelium smooth muscle fascicles in the septa between the lymphatic spaces lymphoid aggregates in the delicate collagenous stroma