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U N I T 5
Circulatory Function
Vascular smooth muscle cells also synthesize colla-
gen, elastin, and other components of the extracellular
matrix; elaborate growth factors and cytokines; and
after vascular injury migrate into the intima and pro-
liferate.
1
Thus, smooth muscle cells are important in
both normal vascular repair and pathologic processes
such as atherosclerosis. The migratory and proliferative
activities of vascular smooth muscle cells are stimulated
by growth promoters and inhibitors, such as platelet-
derived growth factor, thrombin, fibroblast growth fac-
tor, cytokines, and nitric oxide.
Disorders of the Arterial
Circulation
The arterial system distributes blood to all the tissues
in the body. There are three types of arteries: large elas-
tic arteries, including the aorta and its distal branches;
medium-sized arteries, such as the coronary and renal
arteries; and small arteries and arterioles that pass
through the tissues. Each of these different types of
arteries tends to be affected by different disease pro-
cesses. The discussion in this section focuses on hyper-
lipidemia and atherosclerosis, the vasculitides, arterial
disease of the extremities, and arterial aneurysms.
Hyperlipidemia
Hyperlipidemia is a medical condition characterized by
an elevation of any or all lipid profiles and/or lipopro-
teins in the blood. Hyperlipidemias can be classified as
either primary or secondary.
5
Primary hyperlipidemias
are probably genetically based, but the genetic defects
are known for only a minority of patients. Secondary
hyperlipidemia may result from diseases such as diabe-
tes, thyroid disease, renal disorders, liver disorders, and
Cushing syndrome, as well as obesity, alcohol consump-
tion, estrogen administration, and other drug-associated
changes in lipid metabolism. Besides the primary and sec-
ondary hyperlipidemia subtypes, hyperlipidemia is also
classified according to the type of lipid that is elevated—
hypercholesterolemia, hypertriglyceridemia, or both in
combined hyperlipidemia. The condition, specifically
hypercholesteremia, is strongly associated with the
development of atherosclerosis, which causes more
morbidity and mortality in the Western world than any
other disorder. By the year 2025, it is predicted that car-
diovascular mortality will likely exceed that of every
other major disease group including infections, cancer,
and trauma.
6
Lipoprotein Metabolism andTransport
Because lipids, namely cholesterol and triglycerides, are
insoluble in plasma, they are encapsulated by special fat-
carrying proteins called lipoproteins for transport in the
blood. There are five main types of lipoproteins, classi-
fied by their protein content or densities: chylomicrons,
very–low-density lipoprotein (VLDL), intermediate-
density lipoprotein (IDL), low-density lipoprotein (LDL),
and high-density lipoprotein (HDL). Thus, VLDLs carry
large amounts of triglycerides and much less cholesterol
and protein. Low-density lipoprotein is the main carrier
of cholesterol, whereas HDL is about 50% protein and
carries less cholesterol and little triglyceride (Fig. 18-2).
Lipoproteins are macromolecules made up of a hydro-
phobic core of insoluble cholesterol esters and triglycer-
ides, surrounded by a hydrophilic outer shell of soluble
phospholipids, and nonesterified cholesterol
7
(Fig. 18-3).
In addition, the shell contains a variety of apolipopro-
teins, proteins that bind lipids, thereby increasing the
stability and water solubility of the resulting lipopro-
tein. The apolipoproteins also activate certain enzymes
required for normal lipoprotein metabolism, and they
serve as reactive sites that specific receptors on periph-
eral tissues can recognize and use in the endocytosis and
metabolism of the lipoproteins. Apolipoproteins can
be grouped into two classes: exchangeable and nonex-
changeable. Exchangeable apolipoproteins (e.g., apoA-
I, apoC-II, and apoE) are able to dissociate from one
lipoprotein and associate with another, whereas the
nonexchangeable apolipoproteins (e.g., apoB-48 and
SUMMARY CONCEPTS
■■
The walls of blood vessels are composed of an
inner layer of endothelial cells, a middle layer of
vascular smooth muscle, and an outer layer of
loosely woven collagen tissue.
■■
The endothelium, which forms a continuous
lining for the entire vascular system, controls
the transfer of molecules across the vascular
wall and plays a role in the control of platelet
adhesion and blood clotting, modulation of
blood flow and vascular resistance, metabolism
of hormones, regulation of immune and
inflammatory reactions, and elaboration of
factors that influence the growth of other cell
types, particularly the smooth muscle cells.
■■
The term endothelial dysfunction describes
changes in endothelial function that occur in
response to stimuli derived from cardiovascular
risk factors such as smoking, hyperlipidemia,
hypertension, insulin resistance and diabetes, and
obesity.
■■
Vascular smooth muscle cells, which form the
middle layer of blood vessels, control the dilation
and constriction of blood vessels, elaborate
growth factors, and synthesize collagen, elastin,
and other components of the extracellular matrix
that are important in both normal vascular repair
and pathologic processes such as atherosclerosis.
