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Chapter 162. Endothelium in Inflammation and Angiogenesis

Peter Petzelbauer; Robert Loewe; Jordan S. Pober

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Endothelium at a Glance
  • All blood vessel endothelial cells (ECs) perform three important constitutive functions:
    • Maintaining homeostasis of the blood.
    • Forming a barrier that separates circulating blood from the tissue.
    • Regulating the extent of local blood flow.
  • The cutaneous vasculature is divided into a superficial vascular plexus and a deep vascular plexus. The superficial vascular plexus is formed by parallel pairs of arterioles and venules connected via capillary loops that extend into the dermal papillae.
  • ECs participate in innate and adaptive immune responses.
  • Tumor necrosis factor-α and interleukin-1β are important modulators of EC function.
  • Vascular ECs contribute to inflammation through distinctive patterns of adhesion molecule expression. In the skin, E-selectin, vascular adhesion molecule 1, and intercellular adhesion molecule 1 may be particularly important.
  • Microvessels of the skin in situ basally express major histocompatibility complex (MHC) class I and II molecules at their luminal surfaces and may present antigen in an MHC-restricted manner to T cells.
  • In the healthy adult, blood vessels are stable structures with very slow turnover of ECs. In chronic inflammation, tissue injury, wound healing, and tumor growth, new vessels are formed (angiogenesis) and existing vessels undergo remodeling.
  • Keratinocytes produce a wide range of angiogenic factors, including members of the fibroblast or transforming growth factor protein family, platelet-derived growth factor, and vascular endothelial growth factor, as well as chemokines like cutaneous T cell-attracting chemokine. Vascular remodeling is a prominent feature of psoriasis.

The blood vascular system is a continuous series of hollow tubes that carry blood from the heart to the tissues and back again. Blood exits the heart through the aorta that gives rise to a series of diverging, progressively narrower muscular arteries and arterioles, delivering blood to all organs of the body. The terminal arterioles arborize into an interconnecting network of microvessels, mostly capillaries that nourish and cleanse the peripheral tissues. The capillary network empties into a series of converging venules and progressively larger veins that ultimately return the blood to the heart. All segments of this vascular system are lined by a one-cell-thick layer of epithelium-like cells called endothelium (Fig. 162-1). All vascular endothelial cells (ECs) share common features and functions, and hence may be collectively described as one cell type. However, ECs from one segment of the vascular system may differ in significant ways from the ECs at other anatomic sites. Blood vessel ECs differ from lymphatic ECs, which are not discussed in this chapter.

Figure 162-1
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Endothelium. In this postcapillary venule, endothelial cells are seen to line a channel. Nuclei are seen en face and in cross-section, and activated endothelial cells appear to have an edematous cytoplasm, which increases their visibility. This specimen is from an inflammatory lesion (Sweet syndrome; see Chapter 32) without signs of vessel damage.

Blood vessel ECs must perform three important constitutive functions. First, vascular ECs must maintain homeostasis of the blood, which ...

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