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Atherosclerosis and Thrombus Formation
Arterial Wall Injury
 Recent
models of atherogenesis have been based, in part, on the "response-to-injury"
hypothesis proposed by Ross and colleagues [Ross, R. Nature.
1993;362:801]. The concept is that atherosclerosis begins
as a response to chronic minimal injury to the endothelium
(the continuous monolayer of cells lining the arterial wall)
and that interactions among monocytes, lipoproteins, platelets,
lymphocytes, and smooth muscle cells abet and continue the
pathogenic process.
The main "battleground" of the atherosclerotic
process in the intima, which lies just below the endothelium
[Hajjar DP, Nicholson AC. American Scientist. 1995;83:460].
While the media (middle layer) appears to play some role --
and perhaps the adventitia (outer layer) as well -- the development
of atherosclerosis is primarily characterized by an accumulation
of complex lipids, proteins, and carbohydrates, as well as
a proliferation of cells, in the intimal layer of an artery.
Ip and colleagues have proposed a pathophysiologic
classification of vascular injury into three types [Ip JH,
et al, 1990. Ip JH, et al, 1994]. Type I injury, a chronic
minimal injury characterized by functional alterations of
endothelial cells without significant morphologic changes
(i.e., epithelial denudation), is thought to be caused primarily
by the turbulence of blood flow. However, other factors
appear to potentiate endothelial injury, including hypertension,
hypercholesterolemia, circulating vasoactive amines, immunocomplexes,
viral infections, and a chemical irritant in tobacco smoke.
Type II injury is characterized by denuding
of the endothelium and superficial intimal injury. These
changes, which appear to be the result of toxic products released
by accumulating macrophages in the intima, are accompanied
by platelet deposition with or without thrombus formation.
Repetitive Type II injury of soft plaques, with thrombus formation.
Repetitive Type II injury of soft plaques, with thrombus incorporation,
is thought to be a major mechanism for the progression of
atherosclerosis.
Type III injury is typified by deep intimal
and medial damage, accompanied by marked platelet aggregation
and mural thrombosis. Vascular injury of this magnitude
is seen following plaque rupture.
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Stroke Education
