Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Relationship between the Secondary Vascular System and the Lymphatic Vascular System in Fish

Version 1 : Received: 27 December 2023 / Approved: 27 December 2023 / Online: 27 December 2023 (14:46:13 CET)

How to cite: Varaliová, Z.; Panara, V.; Wilting, J.; Koltowska, K.; Jeltsch, M. The Relationship between the Secondary Vascular System and the Lymphatic Vascular System in Fish. Preprints 2023, 2023122119. https://doi.org/10.20944/preprints202312.2119.v1 Varaliová, Z.; Panara, V.; Wilting, J.; Koltowska, K.; Jeltsch, M. The Relationship between the Secondary Vascular System and the Lymphatic Vascular System in Fish. Preprints 2023, 2023122119. https://doi.org/10.20944/preprints202312.2119.v1

Abstract

New technologies have resulted in a better understanding of blood and lymphatic vascular heterogeneity at the cellular and molecular levels. Meanwhile, we still need to learn more about the heterogeneity of the cardiovascular and lymphatic systems between different species at the anatomical and functional levels. Even the deceptively simple question of the functions of fish lymphatic vessels has yet to be conclusively answered. The most common interpretation assumes a similar dual setup of the vasculature in zebrafish and mammals: on the one hand, there is the cardiovascular, circulatory system, and on the other hand, the lymphatic vascular system, in which the unidirectional flow is derived from surplus interstitial fluid and returned into the cardiovascular system. A competing interpretation questions the identity of the lymphatic vessels in fish as at least some of them receive their flow from arteries via specialised anastomoses, neither requiring an interstitial source for the lymphatic flow nor stipulating unidirectionality. In this alternative view, the “fish lymphatics” are a specialised subcompartment of the cardiovascular system, called the “secondary vascular system” (SVS). Many of the contradictions found in the literature appear to stem from the fact that the SVS develops in part or its entirety from an embryonic lymphatic vascular system by transdifferentiation. Future research needs to establish the extent of embryonic transdifferentiation of lymphatics into SVS blood vessels. Similarly, more insight is needed into the molecular regulation of vascular development in fish. Most fish do feature more than the five VEGF genes and three VEGF receptor genes that we know from mice or humans, and the relative tolerance of fish to whole genome and gene duplications could underlie the evolutionary diversification of the vasculature. This review discusses the key elements of the fish lymphatics versus the SVS and attempts to draw a picture coherent with the existing data, including the phylogenetic knowledge.

Keywords

Secondary vascular system; lymphatic vascular system; fish physiology; embryonic development; zebrafish; transdifferentiation; aquatic respiration; cardiovascular system; vascular identity; vascular endothelial growth factors

Subject

Biology and Life Sciences, Anatomy and Physiology

Comments (2)

Comment 1
Received: 31 January 2024
Commenter:
The commenter has declared there is no conflict of interests.
Comment: Very interesting review, and I appreciate the objective and reasonable evaluation of our work presented in Jensen et al, PNAS, 2009 in the context of secondary or lymphatic vascular development and physiology. I would like to clarify a few things brought up in regards to this article in the review:

In their review, Varaliova and Panara et al mention that we did not mention in Jensen et al, PNAS, 2009 if the fish were able to perform active surface respiration (ASR). Indeed, the fish in this study did not have an opportunity for ASR as they were kept in a tube filled with hypoxic water during the hypoxia-stimulation period.

As a comment to the proposed mechanism whereby the secondary vascular system (SVS) in the fins connects to the vascular system when transdifferentiating from the lymphatic system, Jensen et al described the arterial-lymphatic conduits as being present on the thoracic aorta. No ALCs/IAAs could be found on the posterior portion of the aorta, nor any other artery investigated in this study. This may imply that new SVS vessels may have to grow quite far from their position in the fins in order to establish a connection to the aorta in the zebrafish. Also in the transparent glass catfish the IAAs were found on large arteries close to the aorta and relatively far away from the fins.
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Comment 2
Received: 1 February 2024
Commenter:
Commenter's Conflict of Interests: Working in the same lab with Dr Jeltsch.
Comment: This review should definitely also address similar observations in mammals. Most notably the some type of lymphatic-to-blood vessel reprogramming was seen by Chen et al. in 2012 (https://doi.org/10.1172/JCI57513). It is true that the reprogramming seen by Chen et al. was induced by blood flow, whereas the transdifferentiation seen by Das et al. did not require blood flow, but some underlying signalling could still be similar!
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