Page 2074 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 123

THE BLOOD VESSEL WALL

Marianne A. Grant and Aly Karsan

The vasculature plays a major role in conveying and distributing cells contribute to the extracellular matrix (ECM) of the intima,
hematopoietic cells, nutrients, gases, metabolites, and various chemi- along with ECM components including elastin and collagen. 13,14 In
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cal mediators. The interior of the vessel wall is lined by the endo- large vessels, the media is separated from the intima by a layer of
thelium, comprising more than 1012 endothelial cells, covering a elastin, the internal elastic lamina. Diseases associated with mutations
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surface of approximately 500 m and weighing approximately 1 kg in elastin include supravalvular aortic stenosis, 15,16 Williams syn-
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2,3
in total. The endothelium forms a continuous monolayer at the drome, and autosomal dominant cutis laxa. The medial layer is
interface between blood and tissue. Thus it contributes significantly composed primarily of concentric layers of smooth muscle cells and
to sensing and transducing of signals between blood and tissue, their secreted matrix, which is a complex mix of glycoproteins and
trafficking of hematopoietic cells, and maintenance of a nonthrom- proteoglycans. This layer is responsible for the structural integrity of
bogenic surface permitting flow of blood. Normally quiescent with the wall and for maintaining vascular tone. Mutations of the fibrillin-1
cell turnover measured on the order of years, endothelial cells have a gene, a microfilament protein in elastic fibers, result in disruption of
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remarkable capacity to proliferate and vascularize tissues in physiologic the media in Marfan syndrome. Defects of type III collagen can
(menstrual cycle) and pathologic (tumorigenesis, diabetic retino- cause aortic rupture in patients with Ehlers-Danlos syndrome type
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pathy) situations. The endothelium is critical for initiating and IV. An attenuated band of elastic fibers, the external elastic lamina,
potentiating the inflammatory response. The pathogenesis of several separates the adventitia from the media. The adventitia is composed
disorders, such as atherosclerosis, hypertension, diabetic angiopathy, of loose connective tissue, and the outer portion of the media contains
and microangiopathic hemolytic anemias, involves dysfunction of the an ECM scaffold containing fibroblasts, small nerves, progenitor
endothelial lining. The complexity and the vast array of its functional cells, lymphatic vessels, and nutritive blood vessels, the vasa vasorum.
responses have led to the description of the endothelium as a distrib- The adventitia has been recognized as a dynamic environment,
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uted organ. This chapter provides a conceptual framework of the important in the growth, disease, and repair of the artery. The external
structure and development of the vessel wall and the physiologic limit of the adventitial layer is loosely defined and becomes continu-
functions of the endothelium as it relates to the hematopoietic ous with the surrounding connective tissue of the organ. 6,8
system.
Microvasculature
STRUCTURE OF THE VESSEL WALL
Capillaries and postcapillary venules are composed of two cell types:
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The circulatory system has traditionally been divided into the mac- endothelial cells and pericytes. Pericytes and endothelial cells are
rovasculature (vessels >100 µm in diameter) and the microvascula- invested with a basement membrane and, depending on the vascular
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ture. The arterial system transports blood to tissues, resists changes bed, variable amounts of matrix separate the two cell types. Both cell
in blood pressure proximally, and regulates blood flow distally. Veins types contribute to secretion of basement membrane proteins, dem-
return blood to the heart and act as capacitance vessels because they onstrating that pericyte–endothelial interaction plays a key role in
contain approximately 70% of the total blood volume. Venules with basement membrane formation, maintenance, and remodeling. Long
luminal diameters less than 50 µm are structurally similar to capil- pericyte processes extend over the abluminal surface of the endothelial
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laries. Capillaries and microvessels in general are particularly cell, and reciprocal extensions of the endothelial cell make contact
important in the exchange of gases, macromolecules, and cells with the pericyte. At distinct points in the basement membrane,
between blood and tissue. Although large vessels play an important pericytes and endothelial cells form specialized junctions with each
role in maintaining vascular tone, a significant proportion of periph- other. Adherens junctions connect the cytoskeleton of pericytes and
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eral resistance arises from the capillaries. Capillary endothelial cells endothelial cells, mediating contact inhibition through contractile
also have a metabolic role, as in the conversion of angiotensin and forces. Gap junctions between the cytoplasms of pericytes and
hydrolysis of lipoproteins. Finally, sprouting of new vessels is initiated endothelial cells enable communication through the passage of
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in the microvasculature. metabolites and ionic currents. A variety of functions have been
ascribed to the pericyte, including 19,22,23 (1) a contractile function,
which regulates blood flow; (2) multipotential capabilities resulting
Macrovasculature in differentiation to adipocytes, osteoblasts, phagocytes, and smooth
muscle cells; and (3) regulation of capillary growth. The best evidence
Large vessels are composed of three layers: intima, media, and adven- probably exists for the last function. In animal models 24,25 and human
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6,8
titia. The intima comprises the endothelium and the subendothe- disease (diabetic microangiopathy, hemangiomata), a lack of peri-
lium. The endothelial cells of large vessels contain a distinct rod-shaped cytes is associated with microaneurysms and disordered microvascu-
organelle, measuring approximately 3 µm × 0.1 µm, called the lature. In addition, there is a temporal correlation between pericyte
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Weibel-Palade body. Ultrastructural studies indicate the presence of contact and cessation of vessel growth in wound healing, and
a single membrane around the Weibel-Palade body with tubular pericyte contact suppresses endothelial cell migration and prolifera-
structures within. This organelle contains von Willebrand factor tion in vitro. 19
(vWF), and P-selectin has been reported to be present on the sur-
rounding membrane. 10–12 The abluminal face of the endothelium
rests on a basement membrane, which supports the endothelial cell Endothelial Structure and Function
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and can act as a secondary barrier against the extravasation of blood.
The subendothelial matrix contains occasional smooth muscle cells In contrast to circulating blood cells and vascular smooth muscle cells
and scattered macrophages. Both smooth muscle cells and endothelial but similar to epithelial cells, the endothelium exhibits polarity
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