chapter 20
Lipids III: Plasma Lipoproteins
to increased erythrocyte destruction (membrane erythro-
cytes contain increased amounts of cholesterol and phos-
phatidylcholine), proteinuria, and hematuria. The plasma
lipoproteins contain abnormally high amounts of unester-
ified cholesterol and phospholipids, an abnormal lipopro-
tein (Lp-X; see above), VLDL with
-electrophoretic mo-
bility, and two types of abnormal HDL particle.
LCAT deficiency can be selective with regard to the rate
of plasma cholesterol esterification that occurs in VLDL,
LDL, and HDL. In
fisheye disease,
the LCAT activity di-
rected toward VLDL and LDL is normal, whereas LCAT
activity directed toward HDL is absent. Fisheye disease
is characterized by severe corneal opacification beginning
in the teenage years, with eventual bilateral visual impair-
ment. This loss of vision has not been reported in other
instances of corneal opacification. Analysis of the cornea
after transplantation revealed vacuolization of the stroma
and Bowman’s layer and a greatly increased cholesterol
content. Patients with fisheye disease do not exhibit hema-
tological and renal abnormalities, which are characteristic
of familial
LCAT deficiency.
glycerolemia with elevated VLDL and triacylglycerol-
rich LDL accompany
a marked reduction
in HDL
Atherosclerosis and Coronary Heart Disease
Atherosclerosis (athero = fatty and sclerosis = scarring
or hardening) of the coronary and peripheral vasculature
is the leading cause of morbidity and mortality world-
wide. Lesions (called
are initiated by an injury to
endothelium and thicken the intima of arteries, occlude
the lumen, and compromise delivery of nutrients and
oxygen to tissue
Atherosclerotic lesions pri-
marily occur in large and medium-sized elastic and mus-
cular arteries and progress over decades of life. These
lesions cause ischemia, which can result in infarction of
the heart (myocardial infarction) or brain (stroke), as well
as abnormalities of extremities. The proximate cause of
occlusion in these pathological conditions is thrombus
The normal artery wall is composed of three layers: in-
tima, media, and adventita (Figure 20-10). On the luminal
side, the intima contains a single layer of endothelial cells.
These cells permit passage of water and other substances
from blood into tissue cells. On the peripheral side, the
intimal layer is surrounded by a fenestrated sheet of elas-
tic fibers (the internal elastic lamina). The middle portion
of the intimal layer contains various extracellular compo-
nents of connective tissue matrix and fibers and occasional
smooth cells, depending on the type of artery, and the age
and sex of the subject.
Intim a
M edia
elastic lam ina
Sm ooth
m uscle cells
Elastic fibers,
collagen, and
m ucopoly-
External elastic
lam ina
Sm ooth
m u sd o cells
The media is composed of diagonally oriented smooth
muscle cells. They are surrounded by collagen, small elas-
tic fibers, and glycosaminoglycans (proteoglycans). Most
cells are attached to one another by specific junctional
complex, which are arranged as spirals between the elas-
tic fibers and support the arterial wall.
The adventitia is separated from the media by a discon-
tinuous sheet of elastic tissue (the external elastic lamina)
and consists of smooth muscle cells, fibroblasts, colla-
gen fibers, and glycosaminoglycans. This layer is supplied
with blood vessels to provide nutrients.
Atherosclerosis affects mainly the intimal layer. Lesions
occur because of
1. Proliferation of smooth muscle cells,
2. Lipid accumulation in smooth muscle cells and
scavenger cells (resident macrophages and migrant
plasma monocytes), and
3. Connective tissue formation.
Perhaps the most satisfying hypothesis for the forma-
tion of atherosclerotic lesions is that of “response to in-
jury” in which lesions are precipitated by some form of
injury to endothelial cells. The injury may be caused by el-
evated plasma levels of LDL and modified LDL (oxidized
LDL), free radicals (e.g., caused by cigarette smoking),
diabetes mellitus, hypertension-induced shear stress, and
other factors that lead to focal desquamation of endothelial
cells such as elevated plasma homocysteine levels, genetic
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