Blood vessels participate in homeostasis on a moment-to-moment basis and contribute to the pathophysiology of diseases of virtually every organ system. Hence, an understanding of the fundamentals of vascular biology furnishes a foundation for understanding the normal function of all organ systems and many diseases. The smallest blood vessels—capillaries—consist of a monolayer of endothelial cells apposed to a basement membrane, adjacent to occasional smooth-muscle-like cells known as pericytes(Fig. 224-1A). Unlike larger vessels, pericytes do not invest the entire microvessel to form a continuous sheath. Veins and arteries typically have a trilaminar structure (Fig. 224-1B–E). The intima consists of a monolayer of endothelial cells continuous with those of the capillaries. The middle layer, or tunica media, consists of layers of smooth-muscle cells; in veins, the media can contain just a few layers of smooth-muscle cells (Fig. 224-1B). The outer layer, the adventitia, consists of looser extracellular matrix with occasional fibroblasts, mast cells, and nerve terminals. Larger arteries have their own vasculature, the vasa vasorum, which nourishes the outer aspects of the tunica media. The adventitia of many veins surpasses the intima in thickness.
Schematics of the structures of various types of blood vessels. A. Capillaries consist of an endothelial tube in contact with a discontinuous population of pericytes. B. Veins typically have thin medias and thicker adventitias. C. A small muscular artery features a prominent tunica media. D. Larger muscular arteries have a prominent media with smooth-muscle cells embedded in a complex extracellular matrix. E. Larger elastic arteries have cylindrical layers of elastic tissue alternating with concentric rings of smooth-muscle cells.
The tone of muscular arterioles regulates blood pressure and flow through various arterial beds. These smaller arteries have a relatively thick tunica media in relation to the adventitia (Fig. 224-1C). Medium-size muscular arteries similarly contain a prominent tunica media (Fig. 224-1D); atherosclerosis commonly affects this type of muscular artery. The larger elastic arteries have a much more structured tunica media consisting of concentric bands of smooth-muscle cells, interspersed with strata of elastin-rich extracellular matrix sandwiched between layers of smooth-muscle cells (Fig. 224-1E). Larger arteries have a clearly demarcated internal elastic lamina that forms the barrier between the intima and the media. An external elastic lamina demarcates the media of arteries from the surrounding adventitia.
The intima in human arteries often contains occasional resident smooth-muscle cells beneath the monolayer of vascular endothelial cells. The embryonic origin of smooth-muscle cells in various types of artery differs. Some upper-body arterial smooth-muscle cells derive from the neural crest, whereas lower-body arteries generally recruit smooth-muscle cells from neighboring mesodermal structures during development. Derivatives of the proepicardial organ, which gives rise to the epicardial layer of the heart, contribute to the vascular smooth-muscle cells of the coronary arteries. Recent evidence suggests that bone marrow may give rise to both vascular endothelial cells and smooth-muscle cells, particularly under conditions of injury repair or vascular lesion formation. Indeed, the ability of bone marrow to repair an injured endothelial monolayer may contribute to maintenance of vascular health, whereas failure to do so may lead to arterial disease. The precise sources of endothelial and mesenchymal progenitor cells or their stem cell precursors remain the subject of active investigation (Chaps. 65, 66, and 67).
The key cell of the vascular intima, the endothelial cell, has manifold functions in health and disease. Most obviously, the endothelium forms the interface between tissues and the blood compartment. It therefore must regulate the entry of molecules and cells into tissues in a selective manner. The ability of endothelial cells to serve as a selectively permeable barrier fails in many vascular disorders, including atherosclerosis and hypertension. This dysregulation of permeability also occurs in pulmonary edema and other situations of "capillary leak."
The endothelium also participates in the local regulation of blood flow and vascular caliber. Endogenous substances produced by endothelial cells such as prostacyclin, endothelium-derived hyperpolarizing factor, nitric oxide (NO), and hydrogen peroxide (H2O2) provide tonic vasodilatory stimuli under physiologic conditions in vivo (Table 224-1). Impaired production or excess catabolism of NO impairs this endothelium-dependent vasodilator function and may contribute to excessive vasoconstriction in various pathologic situations. By contrast, endothelial cells also produce potent vasoconstrictor substances such as endothelin in a regulated fashion. Excessive production of reactive oxygen species, such as superoxide anion (O2−), by endothelial or smooth-muscle cells under pathologic conditions (e.g., excessive exposure to angiotensin II) can promote local oxidative stress and inactivate NO.
Table 224–1. Endothelial Functions in Health and Disease
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Table 224–1. Endothelial Functions in Health and Disease
|Homeostatic Phenotype||Dysfunctional Phenotype|
|Vasodilation||Impaired dilation, vasoconstriction|
|Antithrombotic, profibrinolytic||Prothrombotic, antifibrinolytic|
|Permselectivity||Impaired barrier function|
The endothelial monolayer contributes critically to inflammatory processes involved in normal host defenses and pathologic states. The normal endothelium resists prolonged contact with blood leukocytes; however, when activated by bacterial products such as endotoxin or proinflammatory cytokines released during infection or injury, endothelial cells express an array of leukocyte adhesion molecules that bind various classes of leukocytes. The endothelial cells appear to recruit selectively ...