Vascular cells adapt to mechanical stimuli and remodel, thereby changing geometry, structure, and properties. Major stresses applied to blood vessels include: (1) axial stress induced by longitudinal tension; (2) circumferential stress (: internal hydraulic radius; h:wall thickness [Laplacian equation for thin, homogeneous wall]) that results from perpendicularly applied blood pressure p _i ; (3) radial compressive stress developed by blood pressure that has a much smaller magnitude with respect to axial and circumferential stresses; and (4) wall shear stress exerted by blood flow at the wetted surface of the vessel wall, i.e., friction on the luminal surface of the endothelium.

Stress distribution within large vessel wall is heterogeneous, as the wall is composed of 3 layers (intima, media, and adventitia) of composite materials. Moreover, stress field bears large temporal and spatial variations, as blood flow is three-dimensional, developing (or unestablished, as flow develops at the entrance of short curved vessels between 2 successive branchings),² and unsteady.³

Elastic properties of vascular wall are usually represented by rheological parameters defined at specific pressures, as the pressure–cross-sectional area relationship is non-linear: (1) either vascular distensibility () or wall compliance and (2) elastic moduli (Vol. 7 – Chap. 5. Rheology). These parameters deal with the bulk wall behavior and do not represent elastic properties of wall material.

Mesodermal cells in the early embryo differentiate into endothelial precursors — angioblasts — and form blood islands. Fusion of blood islands leads to the primary capillary plexi. When blood circulation is established, primary plexi remodel into a hierarchical network of arteries, arterioles, capillaries, venules, and veins.

Vascular smooth myocytes (SMC) are associated with large and mid-sized vessels, whereas capillaries are covered by pericytes. First lymphatic endothelial cells sprout from embryonic veins, then they migrate to form lymphatic sacs. Lymphangiogenesis also involves sprouting, branching, and remodeling. Closed-end lymphatic capillaries drain into collecting vessels and ducts.

The branchial arch artery apparatus is a transient structure that appears in 6- to 7-week-old human embryos. Five branchial arches exist, each of which contains an arch artery (1–4 and 6). Blood exits from the heart via branchial arch arteries to circulate throughout the embryo. The branchial arch artery apparatus is initially symmetrical with equivalent amounts of blood flow through all of these arteries. This arterial apparatus afterward matures and sustains an asymmetrical remodeling. The left fourth and sixth arch arteries persist and generate the aortic arch and pulmonary trunk, whereas the right fourth and sixth branchial arch arteries regress, as blood predominantly flows through the left arch arteries.

This event is concomitant with increased expression of growth factors, such as platelet-derived (PDGF) and vascular endothelial (VEGF) growth factors. It follows rotation and realignment of the ventricular outflow tract that forms part of the left and right ventricles. Outflow tract rotation is required for reshaping of the right sixth arch artery into a long, narrow vessel with reduced blood flow.

The transcription factor pituitary paired-like homeodomain-containing protein Pitx2 (encoded by the homeobox PITX2 gene) stimulated by Nodal, a member of the TGFβ growth factor superfamily involved in cell differentiation, mesoderm formation, and subsequent organization of left–right axial structures, regulates the asymmetric growth. It abounds in cells of the secondary heart field that includes the myocardium of the left wall of the outflow tract. Pitx2 + cells participate to the control of rotation of the outflow tract. Factor Pitx2 is not synthesized in cell types that belongs to or surrounds sixth branchial arch arteries [652]. Although branchial arch artery remodeling requires Pitx2, it is not directly governed by Pitx2 + cells. The anterior heart also requires FGF8 that is overexpressed in the absence of Pitx2 protein. Factor FGF8 may be involved in arch artery maturation. Besides, the Nodal–Pitx2 pathway and abnormal rotation of the outflow tract do not strongly affect branchial arch artery laterality.

Vascular growth factors, such as PDGFa protomer and VEGF, contribute to branchial arch artery apparatus remodeling, as their inhibition specifically yields loss of both left and right sixth arch arteries [652]. Expression of PDGFa is maintained on the left side but decays on the right. The concentration of phosphorylated VEGFR2 in endothelial cells also decreases in the right sixth branchial arch artery, whereas in the case of Pitx2 loss, PDGFa and VEGFR2^P levels remain symmetrical. In addition, ligated left sixth branchial arch artery in 11.5-day-old mouse embryos (before the onset of remodeling; i.e., approximately 35-day-old human embryos) leads to their regression and development of right arteries [652]. In 4 among 6 embryos with ligated left sixth branchial arch artery, PDGFR and VEGFR2^P signalings are reduced on the left side and maintained on the right side. Therefore, hemodynamical stress shapes the asymmetrical arterial system by operating via growth factors.

As blood pulses in an artery, its wall alternatively stretches and recoils. In 1733, S. Hales described blood systolic storage and diastolic restitution. In 1899, O. Frank modeled arterial capacitance by awindkessel element, i.e., a damping air chamber incorporated in a rigid pipe network. Blood vessels are pressure and volume buffers. Veins that are the major blood storage compartments, accommodate volume changes by shrinking to possibly reach a collapse state.

Wall expansion and relaxation depend on the rheology of the vessel wall, and thus on its composition and structure. In particular, distension and subsequent recoil are achieved by the architecture and interactions between coupledelastin andcollagen fibers. In addition to passive caliber changes, the vessel wall undergoes active variations due tovasomotor tone. Vascular smooth muscle activity fits the blood flow to the tissue requirements.

Structural components exist in every kind of blood vessel, except capillaries, although the element amount and structure vary between vessel types.Endothelial cells with a hemodynamic stress-dependent shape (50–100 ×10 ×0.5–2 μm), line the blood–wall interface of the whole vasculature (Chap. 9 ).Smooth myocytes are responsible for vessel tone and hence lumen size (Chap. 8). They thus influence the vascular impedance.

Specific cells of connective tissue (Vol. 1 – Chap. 1. Cells and Tissues) includefibroblasts (FB; Vol. 1 – Chap. 2. Cells of the Blood Circulation)) that produce ground matrix and fibers in growing tissues andfibrocytes (FC). The ground matrix fills the space between cells and fibers. It is composed of interstitial fluid that contains electrolytes and plasma molecules,proteoglycans, and glycoproteins. Elastin forms low-stiffness elastic fibers, taut in the unstretched configuration that can stretch up to 60% with elastic behavior. Collagen makes high-stiffness fibers that are tortuous in the unstretched configuration and are responsible for structural integrity. Thereby, elastin provides vessel distensibility and collagen tensile strength.⁴

The wall structure is characterized by a tunica set that comprises intima, media, and external adventitia in large arteries and veins (Fig. 7.1). Tunica number and structure vary according to vessel type and size.

Vascular endothelial cells in the central nervous system form a barrier that restricts molecule fluxes between the blood and brain. Thisblood–brain barrier (BBB) ensures proper neuronal functioning and protects the central nervous system (CNS). The blood–brain barrier results from interactions between endothelial cells and neural cells. Its main constituents include endothelial cells, astrocytes, and pericytes, in addition to the extracellular matrix.

The average distance fromcapillary to neuron ranges from 8 to 20 μm. The microvasculature of the central nervous system is aimed, in addition to its usual goals, at maintaining the homeostasis of the internal medium. A constant microenvironment is indeed required for neuronal activity.

The blood–brain barrier was first described by P. Ehrlich in 1903. It corresponds to a specialized endothelium of cerebral capillaries that avoids any fluctuation in substance concentration in the extracellular space, especially ions, whereas blood supplies the brain with the required nutrients (Fig. 7.5). Unlike peripheral capillaries that allow substance filtration across and between endothelial cells, the blood–brain barrier strictly limits transport into the brain through cerebral microvascular endothelial cells sealed by tight junctions¹⁸ (Vol. 1 – Chap. 7. Plasma Membrane) and plasmalemmal carriers. The endothelial cells of the blood–brain barrier are characterized by transport restriction due to tight junctions and polarized carriers, as well as unique metabolic properties.

Walls of cerebral capillary is thinner than that of the muscle capillary [668]. The wall thickness could modulate the restrictive permeability of the blood–brain barrier with a shorter transendothelium transport time. A greater mitochondrion number might exist in BBB endothelial cells than in other endothelial cells, in relation to energy-dependent transcapillary transport [669].

The restrictive blood–brain barrier with its enzymes and transporters develops during embryogenesis. Endothelial cells characterized by a reduced vesicular transport form nascent vessels in the central nervous system to which pericytes are recruited, before astrocytes are generated [678].Pericytes regulate the function and proper structure of the blood–brain barrier, in particular the formation of tight junctions and vesicle transfer in endothelial cells of the central nervous system [678]. They inhibit the expression of molecules that increase vascular permeability and immunocyte infiltration. Pericytes reduces the permeability of the blood–brain barrier to water and low- and high-molecular-mass molecules [671]. In addition, pericytes may mediate the attachment of astrocyte end-feet to endothelial cells [671].The PDGFb–PDGFRβ complex is required in pericyte recruitment during angiogenesis.