Figure 125

Diagram depicting segments of two adjacent endothelial cells. This diagram shows cell-to-cell and cell-to-extracellular matrix junctions represented here by the junctional complex and hemidesmosomes, respectively. Observe the organization of the cytoplasm and cytoplasmic inclusion, the Weibel-Palade bodies that are characteristic of endothelial cells. Plnocytotic vesicles in the cell on the left have been positioned to suggest the pathway of vesicles from the lumen of the blood vessel to the basal cell membrane or to the lateral cell membrane as indicated by the dashed arrows. Various markers have been traced through pinocytotic pathways across the endothelial cell. (Modified from Rhodin JAG. Handbook of Physiology. New York: Oxford University Press, 1980.)

microvilli

Weibel-Palade body luminal surface of endothelium junctional complex

vesicles connective ;—r" tissue lamina hemidesmosomes microvilli vesicles connective ;—r" tissue lamina

Weibel-Palade body hemidesmosomes luminal surface of endothelium junctional complex table 12.2. Summary of Endothelial Cell Properties and Functions

Major Properties

Maintenance of selective permeability barrier

Maintenance of nonthrombo-genic barrier

Modulation of blood flow and vascular resistance

Regulation of cell growth

Regulation of immune responses

Maintenance of extracellular matrix

Involvement in lipoprotein metabolism

Associated Functions

Active Molecules Involved

Simple diffusion Active transport Pinocytosis

Receptor-mediated endocytosis

Secretion of anticoagulants Secretion of antithrombogenic agents

Secretion of prothrombogenic agents

Secretion of vasoconstrictors Secretion of vasodilators

Secretion of growth-stimulating factors

Secretion of growth-inhibiting factors

Regulation of leukocyte migration by expression of adhesion molecules Regulation of immune functions

Synthesis of basal lamina Synthesis of glycocalyx

Production of free radicals

Oxygen, carbon dioxide

Glucose, amino acids, electrolytes

Water, small molecules, soluble proteins

LDL, cholesterol, transferrin, growth factors, antibodies,

MHC complexes

Thrombomodulin,

Prostacyclin (PGI2), tissue plasminogen activator (TPA), an-tithrombin III, heparin

Tissue thromboplastin, von Willebrand factor, plasminogen activator inhibitor

Endothelin, angiotensin-converting enzyme (ACE) Endothelial derived relaxation factor (EDRF)/nitric oxide (NO), prostacyclin

Platelet-derived growth factor (PDGF), hemopoietic colony stimulating factors (GM-CSF, G-CSF, M-CSF)

Heparin, transforming growth factor (3 (TGF/3)

Selectins, integrins, CD marker molecules

Interleukin molecules (1L-1,1L-6,1L-8), MHC molecules

Type IV collagen, laminin Proteoglycans

LDL, cholesterol, VLDL

Modified from Cotran S, Kumar V, Collins T, Robbins SL, eds. Robbins Pathologic Basis of Disease. Philadelphia: WB Saunders, 1999.

acids, and electrolytes) can diffuse or are actively transported across the plasma membrane and released into the extracellular space. Small molecules, water, and soluble proteins are transported by pinocytotic vesicles (a clathrin-independent form of endocytosis). Small but numerous, pinocytotic vesicles transport bulk material from the blood into the cell. Larger molecules are transported through fenestrations within the endothelial cells visible in transmission electron microscope (TEM) preparations. These fenestrations are believed to be the morphologic equivalents of the "large pores" described by physiologists. In addition, some specific molecules (e.g., low-density lipoprotein (LDL), cholesterol, transferrin) are transported via receptor-mediated endocytosis (a clathrin-dependent process), which uses endothelial specific surface receptors.

• Maintenance of a nonthrombogenic barrier between blood platelets and subendothelial tissue by producing anticoagulants (thrombomodulin and others) and antithrombogenic substances (prostacyclin [PGL] and tissue plasminogen activator). Damage to endothelial cells causes them to release prothrombogenic agents (von Willebrand factor, plasminogen activator inhibitor). These agents cause platelets to aggregate and release factors that result in the formation of clots or masses, called thrombi, that potentially prevent blood loss.

• Modulation of blood flow and vascular resistance by secretion of vasoconstrictors (endothelin, angiotensin-

converting enzyme) and vasodilators (EDRF/NO, prostacyclin).

• Regulation and modulation of immune responses by controlling interaction of lymphocytes with the endothelial surface, which is mainly achieved by the expression of adhesion molecules and their receptors on the endothelial free surface as well by secretion of three classes of interleukins (IL-1, IL-6, and IL-8).

• Hormonal synthesis and other metabolic activities by synthesis and secretion of various growth factors (hemopoietic colony-stimulating factors [CSFs], such as granulocyte-macrophage CSF [GM-CSF1, G-CSF, and M-CSF; fibroblast growth factor (FGF); and platelet-derived growth factor (PDGF)J. Endothelial cells also synthesize growth inhibitors such as heparin and transforming growth factor ß (TGF-/3). Endothelial cells function in the conversion of angiotensin I to angiotensin II in the renin-angiotensin system that controls blood pressure, as well as in the inactivation or conversion of a number of compounds conveyed in the blood (norepinephrine, thrombin, prostaglandins, bradykinin, and serotonin) to inactive forms.

• Modification of the lipoproteins by oxidation. Lipoproteins, mainly LDLs with a high cholesterol content and very low density lipoproteins (VLDLs), are oxidized by free radicals produced by endothelial cells. Modified LDLs, in turn, are rapidly endocytosed by macrophages, forming foam cells (Fig. 12.6). Foam cells are a charac monocyte

cell adhesion molecules endothelium tunica intima internal elastic membrane tunica media smooth muscle cells

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