C h a p t e r 1 8
Disorders of Blood Flow and Blood Pressure
403
Endothelial Cells
Endothelial cells form a continuous lining for the entire
vascular system called the
endothelium.
Once thought
to be nothing more than a lining for blood vessels, it is
now known that the endothelium is a versatile, multi-
functional tissue that plays an active role in controlling
vascular function
1–4
(Table 18-1). As a selectively perme-
able monolayer, the endothelium controls the transfer
of molecules across the vessel wall. The endothelium
also plays a role in the modulation of blood flow and
vascular resistance; control of platelet adhesion and
blood clotting; metabolism of hormones; regulation of
immune and inflammatory reactions; and elaboration
of factors that influence the growth of other cell types,
especially vascular smooth muscle cells.
Structurally intact endothelial cells respond to vari-
ous abnormal stimuli by adjusting their usual functions
and by expressing newly acquired functions.
1
The term
endothelial dysfunction
describes several types of poten-
tially reversible changes in endothelial function that
occur in response to environmental stimuli. Endothelial
cell dysfunction has been implicated in a number of
pathologies including thrombosis, atherosclerosis, and
hypertensive vascular lesions.
3,4
There is also evidence
that the dysfunction contributes to conditions such as
erectile dysfunction, disorders of the retina, kidney dis-
ease, pulmonary hypertension, and septic shock.
Inducers of endothelial dysfunction include cardio-
vascular risk factors such as smoking, hyperlipidemia,
hypertension, insulin resistance and diabetes, and aging
that contribute to the development of atherosclerosis.
Dysfunctional endothelial cells, in turn, produce pro-
inflammatory cytokines, growth factors (e.g., vascular
endothelial growth factor), reactive oxygen species, pro-
coagulant or anticoagulant substances, and a variety of
other disease-producing products. They also influence
the reactivity of underlying smooth muscle cells through
production of both relaxing factors (e.g., nitric oxide) and
contracting factors (e.g., endothelins; see Chapter 17).
Vascular Smooth Muscle Cells
Vascular smooth muscle cells, which form the predomi-
nant cellular layer in the tunica media, produce vasocon-
striction or vasodilation. A network of vasomotor nerves
of the sympathetic component of the autonomic nervous
system supplies the smooth muscle in the blood vessels.
These nerves are responsible for constriction of the vessel
walls. Because they do not enter the tunica media of the
blood vessel, the nerves do not synapse directly on the
smooth muscle cells. Instead, they release the neurotrans-
mitter norepinephrine, which diffuses into the media and
acts on the nearby smooth muscle cells. The resulting
impulses are propagated along the smooth muscle cells,
causing contraction of the entire smooth muscle cell
layer and thus reducing the radius of the vessel lumen.
Tunica externa
(outer coat)
Tunica media
(middle coat)
Tunica intima
(inner coat)
Lumen
Endothelial
cells
Connective
tissue
Internal elastic
membrane
Smooth
muscle cell
Collagen and
elastic fibers
FIGURE 18-1.
Diagram of a typical artery showing the tunica
externa, tunica media, and tunica intima.
TABLE 18-1
Endothelial Cell Properties and Functions
Major Properties
Associated Functions/Factors
Maintenance of a selectively permeable barrier
Controls the transfer of small and large molecules across the vessel wall
Regulation of thrombosis
Elaboration of pro- and antithrombotic molecules (vonWillebrand factor,
plasminogen activator) and antithrombotic molecules (prostacyclin,
heparin-like molecules, plasminogen activator)
Modulation of blood flow and vascular reactivity Elaboration of vasodilators (nitric oxide, prostacyclin) and vasoconstrictors
(endothelins, angiotensin-converting enzyme)
Regulation of cell growth, particularly smooth
muscle cells
Production of growth-stimulating factors (platelet-derived growth factor,
hematopoietic colony-stimulating factor) and growth-inhibiting factors
(heparin, transforming growth factor-
β
)
Regulation of inflammatory/immune responses Expression of adhesion molecules that regulate leukocyte migration and
release of inflammatory and immune system mediators (e.g., interleukins,
interferons)
Maintenance of the extracellular matrix
Synthesis of collagen, laminin, proteoglycans
Involvement in lipoprotein metabolism
Oxidation of very low density lipoproteins, low density lipoproteins, and
cholesterol
Data from Schoen FJ. Blood vessels. In: Kumar V, Abbas AK, Fausto N, et al; eds. Robbins and Cotran
Pathologic Basis of Disease, 8th ed. Philadelphia, PA: Saunders Elsevier; 2010:490–491; Ross MH, PawlinaW.
Histology: AText and Atlas, 6th ed. Philadelphia, PA: Wolters Kluwer | Lippincott Williams &Wilkins;
2011:412–414.
