Page 141 - Cardiac Nursing

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C HAPTER 5 / Atherosclerosis, Inflammation, and Acute Coronary Syndrome 117
to years) results in the progressive narrowing of the arterial lumen. stages of atherosclerosis, which contribute to more avid cellular
Thrombus remnants contain increasing numbers of smooth mus- lipoprotein recruitment. 70–72 Dermatan sulfate proteoglycans are
cle cells derived by ingrowth from the intima. These smooth mus- another surface moiety hypothesized to increase the rate of pro-
cle cells synthesize collagen, providing the stratum for overgrowth gression of atherosclerosis. 72 This class of molecules also binds
of endothelial cells at the lumen. Ultimately, thrombi may con- plasma LDL under physiological conditions with increased affin-
tinue to enlarge, with the potential to rapidly occlude the lumen ity in comparison with other molecules of this class. 73 In vitro
of a medium-sized artery (within days or even hours). studies of smooth muscle cells exposed to conditioned media from
Several mechanisms can influence the location, frequency, con- cultured macrophages provides evidence for a role for
centration, and size of thrombi. Shear stress participates in lesion macrophages in modulating the type and amount of proteogly-
progression, with thrombotic occlusions being common at vessel cans found in the developing lesion. 74 Macrophage accumulation
bifurcations and locations of arterial angulation. 56 Increased lev- in type II lesions leads to the production of enzymes capable of
els of low-density lipoproteins (LDLs) (demonstrated to impair degrading proteoglycans within the lesion locale. Enzymatic di-
platelet function), 57,58 nutrition, 59 contents of cigarette smoke, 60 gestion of the chondroitin sulfate proteoglycan, versican, leads to
and elevated lipoprotein(a) levels 61,62 have been associated with progression of the lesion because of its role in maintaining the vis-
greater risk for clinical coronary artery disease. Taken together, coelasticity and the integrity of the vessel wall against the passage
systemic factors play a significant role in modulating the develop- of plasma materials.
ment of thrombi. Although there are significant decreases in elastin content in
advanced atherosclerotic lesions, few changes are reported in ini-
Atherosclerotic Aneurysms tial and fatty streak lesions. A variety of elastases attack elastic
A common sequela of advanced lesions (types IV, V, and VI) is the fibers, and the possibility exists for macrophages 75 and smooth
76
development of distensions in the entire vascular wall. These muscle cells to produce such proteases. This results in a decrease
aneurysms are most commonly associated with type VI lesions, in structural integrity. Moreover, degradation of elastic fibers may
when the intimal surface is eroded. Both old and new mural have significant consequences in early lesions, because elastin-de-
thrombi permeate atherosclerotic aneurysms, and the thrombi be- rived peptides are extremely chemotactic for macrophages. The
come layered in older aneurysms. Whereas the thrombi can form component cells and extracellular matrix of the atherosclerotic le-
large masses that can fill an aneurysm, the underlying lumen re- sion are reviewed briefly below.
mains generally well preserved and approximates the dimensions
of the original vessel. The evolution of atherosclerotic aneurysms Smooth Muscle Cells
is preceded by a series of changes in the locale of the lesion. Ma- Alterations in the functional properties and amount of smooth
trix fibers are continuously degraded and resynthesized, 63 causing muscle cells are a central feature of atherogenesis. Changes result
a progressive decay of matrix architecture that results in dilation from stimuli, including lipid accumulation, disruption of intimal
and potentially rupture. 64 Susceptibility to atherosclerotic structure, damage to intimal cells and matrix, and deposits of
aneurysm is modulated by secondary risk factors resulting in in- platelets and fibrinogen. These stimuli activate resident cells to
creased hemodynamic and/or tensile stress (e.g., hypertension) produce mitogenic factors, spurring smooth muscle cell prolifera-
and by genetic variation. The search for genetic factors predispos- tion, and ultimately contributing to lesion progression.
ing to atherosclerotic aneurysm development is ongoing.
Macrophages
Severity of Stenosis Whereas macrophages are generally located proximal to the lu-
The severity of lesion stenosis modulates the degree of impaired men, foam cells are trapped within the intima. However, this dis-
blood flow. The degree of stenosis is estimated by the ratio of the tribution becomes less obvious in complicated lesions or regions
maximum diameter of a stenosed artery in comparison to an adja- in which the intima is relatively thin. When a lipid core is present,
cent normal arterial diameter. Coronary artery blood flow begins macrophage foam cells are usually most evident along the luminal
to decrease to a clinically significant degree with 50% stenosis and aspect and at the lateral margins of the core. Macrophage foam
65
blood flow decreases rapidly when stenosis exceeds 70%, and the cells are more numerous and found closer to the surface of the le-
determination of stenosis is of particular clinical benefit above and sion boarder, largely because of a lack of intimal thickening at the
below these cutoffs. However, this physiological marker (decrease lesion periphery. Foam cells eventually die as the lesion develops,
in blood flow) is technically difficult to measure accurately and fails contributing to the growth of what is more appropriately termed
to account for other factors that can influence the clinical impact a “necrotic” core, being composed of extracellular lipid and necro-
of stenosis on a patient (e.g., rate of lesion growth and lesion length tizing cells. Unfortunately, there are currently no appropriate bio-
and/or geometry). 66 Nevertheless, percent stenosis measured by a markers for defining this type of cellular injury.
variety of means provides a powerful tool with significant clinical An accumulating body of evidence indicates that in addition
usefulness in the evaluation of coronary disease. 67–69 to lipid accumulation, macrophages contribute to atherogenesis
by secretion of a range of factors modulating the formation and
Cells and Extracellular modeling of advanced lesions, including monocyte chemotactic
Matrix of Lesions protein-1 and tumor necrosis factor (TNF). 77 Lesions laden with
monocytes and macrophage foam cells 42,43 are more prone to rup-
A host of changes exist in the cellular compartment and extracel- ture because of the release of proteolytic enzymes (e.g., collagenase
lular matrix composition of lesions. Interaction of the apolipopro- and elastase) by the macrophages. It is not clear yet if macrophages
tein B on LDL with cell surface glycosaminoglycans appears to be secrete these enzymes throughout lesion formation or only as they
a mechanism for trapping LDL in the arterial intima. Moreover, die. The capacity of macrophages to express cytokines and growth
production of glycosaminoglycans increases during the early regulatory molecules was reviewed earlier. 31