Page 142 - Cardiac Nursing

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118 PA R T I I / Physiologic and Pathologic Responses
Lymphocytes properties. Functions attributed to specific oligosaccharides
Monoclonal antibodies against CD antigens reveal the presence of include antiproliferative effects on arterial smooth muscle cells, 88
T (CD4
T helper and CD8
T killer) and B lymphocytes in fibroblast growth factor binding, 89,90 lipoprotein lipase binding, 91
advanced lesions. 78 It is yet unclear to what extent these immune and antithrombin III binding. 92 While hypotheses regarding the
cells participate in the atherogenic process. Macrophage foam cell- concentrations, composition, and function of various proteogy-
derived oxidized lipids constitute a significant but variable com- clans are currently being evaluated, the lack of clinical studies to
ponent of the core of advanced lesions. 79–81 Autoantibodies that inform the clinical relevance of such hypotheses makes discussion
recognize oxidized LDL have been isolated from human sera, 82 of these molecules premature in this venue.
and the titers of these antibodies may potentially be diagnostic of
advanced atherosclerosis. 83 In addition, viral and bacterial (e.g., Collagen
chlamydia) antigens have been found in advanced human lesions Second only to lipids, collagen is the major extracellular compo-
using molecular and immunocytochemical techniques. 84 nent of type V lesions. The increased collagen of atherosclerotic le-
sions is produced by intimal smooth muscle cells. The major col-
Lipid and Lipoprotein in the lagen type of advanced lesions is the fibrillar collagen type I. Type
Extracellular Matrix I collagen is particularly prevalent in the fibrous cap and in vascu-
While the transfer of lipoproteins from the plasma into the intima larized regions of advanced lesions. 93 A significant and consistent
is a physiological process, the concentrations of these particles are change in the minor collagen types of advanced atherosclerotic
particularly elevated in advanced lesions. 33 Definitive identifica- lesions includes type V collagen, which increases with advancing
97
tion of the types and amounts of extracellular lipid are difficult fibrosis 94–96 and plays a role in cell migration ; and type IV colla-
and depend largely on methods of tissue preparation and study. gen, which is associated with the basement membranes of smooth
More extracellular lipid is observed in lesion types III, IV, Va, and muscle cells. The exact stimulus for collagen accumulation in ath-
VI. In addition, extracellular lipid accumulates and pools, form- erosclerosis is unknown, although redistribution of mechanical
ing “lipid cores,” in lesion types IV, Va, and VI. Lesions contain stress has been shown to produce changes in matrix production.
many lipid-laden cells that die or can be found in various stages of
disintegration, evidence that much of the extracellular lipid is de- Elastin
rived from cells and lipoproteins originally internalized by The relative concentration and localization of elastin fibers varies
cells. 79,80 In addition, intracytoplasmic lipid can also be expelled with the location and type of lesion. De novo synthesis of suben-
from intact cells into the extracellular space. 85 Extracellular lipid dothelial, medial, and adventitial elastin is common in type V
is also derived in part by direct coalescence of plasma-derived lesions, along with collagen. Whereas the smooth muscle cells of
lipoproteins. 86,87 advanced lesions produce elastin, integration of the protein into a
functional elastic fiber may be impaired.
Fibrinogen Split or frayed elastic fibers tend to associate closely with lipid
The degree and extent to which fibrinogen accumulates in ad- and calcium deposits. Lipid bound to elastic fibers may change
vanced lesions or parts of advanced lesions varies. Immunohisto- elasticity of tissue by modifying the functionality of the elastin
chemical techniques show that the cores of advanced lesions stain fibers and increase their susceptibility to proteolytic degrada-
for fibrinogen more than any other part of advanced lesions, ex- tion. 98,99 Both calcium and magnesium may increase the degra-
cept superimposed thrombi. It must be recalled that immunohis- dation of elastin, 100 the degradation products of which have been
tochemical staining alone cannot distinguish thrombus-associated reported to produce chemotactic derivatives, which recruit
fibrinogen from physiological infiltration of fibrinogen from the macrophages. 101
plasma. However, it is generally accepted that intensely fibrino-
gen-positive bands found in the majority of advanced lesions con- Calcium
stitute evidence of incorporated past thrombi. 55 Fibrinogen con- Mineralization of atherosclerotic lesions is a well-substantiated
tributes directly and indirectly (by promoting smooth muscle cell phenomenon. Accumulation of calcium in the arterial wall in the
growth) to the volume of most advanced lesions. course of the atherogenic process is considered to be a manifesta-
tion of advanced atherosclerosis. Unfortunately, very little is
Proteoglycans known about the factors controlling the quantity of calcium in the
Proteoglycans are a class of glycosylated proteins that have cova- lesions. Vesicles in the extracellular matrix of advanced lesions
lently linked sulfated glycosaminoglycans, (i.e., chondroitin sul- may serve as sites for calcification. 102 Mineral deposits in athero-
fate, dermatan sulfate, heparan sulfate, heparin). The protein sclerosis may also be associated with elastic fibers. 103
component of proteoglycans is a core protein that is modified by
the addition of a complex set of sugar groups. Glycosaminogly- Inflammation
cans are sulfated polysaccharides made of repeating disaccharides
(40 to 100 repeats, on average). These complex groups endow Epidemiological research in cohort studies over the past three
proteoglycans with unique properties. In contrast to arterial gly- decades (e.g., the Framingham Heart Study and the Multiple Risk
cosaminoglycans, little is known about qualitative changes in spe- Factor Intervention Trial) has resulted in the elucidation of several
cific proteoglycan molecules in atherosclerotic lesions. Large ex- risk factors for cardiovascular disease (CVD). 104,105 Such studies
tracellular proteoglycans, mainly chondroitin sulfate-containing have established the following risk factors for CVD: age, male
molecules, function in arterial permeability, ion exchange, trans- gender, hypertension, diabetes mellitus, dyslipidemia, and smok-
port, and deposition of plasma materials such as LDL. Extracellu- ing. Strong evidence also exists to implicate lack of physical activ-
lar heparin sulfate proteoglycans possessing particular oligosac- ity, obesity, and alcohol intake. While recognition and control of
charide or carbohydrate sequences have different functional these risk factors have engendered a substantial reduction in