New Insights on the Development of the Vascular System

By Domenico Ribatti

New Insights on the Development of the Vascular System examines the most recent literature and data on the development of the vascular system, along with advice on new laboratory techniques and approaches to data analysis. This volume is a comprehensive handbook to the state-of-the-art in vascular system development. Several genetic and epigenetic mechanisms are involved in the early development of the vascular system, and there is extensive literature on the genetic background and molecular mechanisms responsible for blood vessel formation. Yet new data and techniques have been developed in recent years.

Although scientific literature covers the descriptive aspects of embryonic vascular system development, modern techniques such as the technology of cell fusion, cell sorting and image analysis give new insight into the mechanisms by which vessels form and regress and how blood flow changes directions in the same vessels.

• Gives a comprehensive overview of the most recent literature in the field of vascular system development
• Presents new data, including sections on endothelial cell signaling and technologies of cell fusion, cell sorting and image analysis
• Provides useful insights on the analysis of new experimental work
• Suggests modern techniques for scientists to use in the lab
• Gives an overview of vascular biology that will be useful for those needing rapid familiarity
• Provides an expert guide to the state-of-the-art in vascular system development as written by a leader in the field

• Language: English
• Publisher: Academic Press
• Release date: Jun 2, 2022
• ISBN: 9780323915793

Domenico Ribatti

Domenico Ribatti was awarded his M.D. degree in October 1981, with full marks. In 1983, D.R. joined the Medical School as Assistant at the Institute of Human Anatomy, University of Bari. In 1984, he took the specialization in Allergology. In 1989, he spent one year in Geneva, working at the Department of Morphology (Prof. R. Montesano). In 2008, he received the honoris causa degree in Medicine and Pharmacy form the University of Timisoara (Romania). D.R. is author of 866 publications as reported in PUBmed and contributed to 50 chapters to books. Overall, his papers have been cited 51153 times. He has published many books with both Elsevier and Springe

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Chapter 1: Introduction

Abstract

William Harvey (1578–1657) established the modern functional definition of the circulatory system in the 17th century, describing how the arteries and veins carry blood away from and toward the heart in a continuous circulation (Ribatti, 2009). Harvey refuted the Galenic physiology of the formation of the blood in the liver and its consumption within organs. In his publication, Exercitatio anatomica de motu cordis et sanguinis in animalibus (Harvey, 1628), he postulated the existence of a circulatory movement of the blood (Harvey, 1963). He found support from Marcello Malpighi (1628–1694), who described capillaries in the lung and the frog mesentery (Brown and Barnes, 1994).

Keywords

Circulatory system; Continuous circulation; Blood; Liver; Homeostasis; Frog mesentery

William Harvey established the modern functional definition of the circulatory system in the 17th century, describing how the arteries and veins carry blood away from and toward the heart in a continuous circulation (Fig. 1) (Ribatti, 2009). Harvey refuted the Galenic physiology of the formation of the blood in the liver and its consumption within organs. In his publication, Exercitatio anatomica de motu cordis et sanguinis in animalibus (Harvey, 1628), he postulated the existence of a circulatory movement of the blood (Harvey, 1963). He found support from Marcello Malpighi, who described capillaries in the lung and the frog mesentery (Brown and Barnes, 1994).

Fig. 1

Fig. 1 A portrait of William Harvey. (Reproduced from Ribatti D: William Harvey and the discovery of circulation of the blood, J Angiogenes Res 1:3, 2009.)

In the early 20th century, pioneering vascular embryologists, such as Florence Sabin, used careful examination of developing blood vessels to provide detailed anatomical descriptions of the formation of the earliest blood vessels in different mammalian species.

The cardiovascular system consists of the heart and an interconnected network of blood vessels, including the arteries, veins, and capillaries. The arteries and veins are classified on the basis of their size and location within the vascular tree.

The formation of the cardiovascular system is one of the earliest events to occur during embryonic development, and the vertebrate heart is the first organ to become functional and is controlled by both genetic and epigenetic (environmental) factors. The heart develops from the precardiac lateral folds derived from presumptive mesodermal cells to form the primitive heart tube, consisting of an inner endothelium, which is separated from the outer myocardial tube by the elastic cardiac jelly. Emergence of the cardiac endothelium and cardiomyocytes occurs almost concomitantly, and, at first, they develop rather independently from one another (Sugy and Markwald, 1996). The endocardium is continuous with the endothelium of the major blood vessels, the axial vein, and the dorsal aorta. Complex asymmetric morphogenetic movements coupled with uneven growth rates contribute to looping and chamber formation (Fig. 2).

Fig. 2

Fig. 2 The heart originates from mesodermal cells in the primitive streak. During gastrulation, cardiac progenitors migrate to the splanchnic mesoderm to form the cardiac crescent. At E7.5 in the mouse, the cardiac crescent can be divided into two heart field lineages based on differential gene expression and their respective contribution to the heart, namely, a first heart field (red) and a second heart field (yellow) , which are located posteriorly and medially to the first heart field. At E8.0, the linear heart tube is present. At E8.5, the looping is associated with uneven growth of cardiac chambers. The outflow tract is at the arterial pole, and the inflow tract and primitive atria are at the venous pole. By E9.5, the common atrium has moved superior to the ventricles and is separated by a distinct atrioventricular canal. By E10.5, cardiac neural crest cells from the dorsal neural tube migrate via the pharyngeal arches to the cardiac outflow tract. Further cardiac development involves a series of septation events and myocardial trabeculation that result in a mature four-chambered heart integrated with the circulatory system depicted at E15.5. (Reproduced from Epstein JA, Aghajanian H, Singh MK: Semaphorin signaling in cardiovascular development, Cell Metab 21:163–173, 2015.)

The cardiovascular system has evolved to service the function of gas exchange, nutrient delivery, and waste product removal and contributes to the control of temperature and pressure/perfusion through vasoconstriction and vasodilation. The principal function of the circulatory system remains to maintain oxygen homeostasis by modulating oxygen delivery within every tissue (Fig. 3). Several genetic, microenvironmental, and epigenetic mechanisms are involved in the early development of the vascular system.

Fig. 3

Fig. 3 Circulatory systems in multicellular organisms. (A) In arthropods and mollusks, the organs are surrounded by the hemolymph. The heart pumps the hemolymph into the open hemocoel from where it is retrieved back into the heart (arrows). (a) The vascular system is lined with a layer of cardioblasts and a luminal basement membrane. The hemolymph contains hemocytes. (B) In annelids, cephalopods, holothurians, and amphioxus, the blood is located in a closed vascular system. The latter consists of blood vessels in which the blood is pumped by contractile myoepithelial cells. (b) The vessels are lined by the basement membrane of mesothelial cells and/or intestinal cells. Hemocytes occur free in the vessel lumen and adherent at the luminal basement membrane. (C) In vertebrates, the circulatory system is closed. The blood is pumped through the whole organism by the heart. Arrows indicate the direction of blood flow. (c) The vasculature is lined by the apical cell surface of endothelial cells. The vascular basement membrane is abluminally located. Peripheral mural cells are located basally, within or at the basement membrane, and stabilize the vessels. The blood mainly contains red blood cells, besides leukocytes and thrombocytes. (Reproduced from Strilic B, Eglinger J, Krieg GM, et al.: Electrostatic cell surface repulsion initiates lumen formation in developing blood vessels, Curr Biol 20: 2003–2009, 2010.)

Vascular development and homeostasis are underpinned by two fundamental features: the generation of new vessels to meet the metabolic demands of underperfused regions and the elimination of vessels that do not sustain flow. The generation of blood vessels was first described through careful observations of living amphibian or avian embryos (Clark, 1918; Sabin, 1917, 1920).

In 1878, Wilhelm Roux postulated that vascular development proceeds in three phases: a stage of primary differentiation founded on hereditary principles, a transitional stage wherein the genetic elements are gradually supplanted by functional adaptation, and a final stage wherein further vascular development is entirely regulated by mechanical forces (Roux, 1878).

Angiogenesis, describing the development of microvessels from preexisting ones, was recognized as early as 1794, when John Hunter in his Treatise on the blood, inflammation and gunshot wounds described the formation of vessels in the chick embryo (Fig. 4) (Hunter, 1794). He stated that vessels would appear to have more powers of perfecting themselves, when injured, tan any other part of the body; for their use is almost immediate and constant, and it is they which perform the operation on the other parts, therefore they themselves must be perfect. (Hunter,