| 
Atherosclerosis and Thrombus Formation
Role of Monocytes and T-Lymphocytes in the Transformation
to Foam Cells
 Adhesion
of circulating monocytes (white blood cells that become particle-ingesting
macrophages once they enter another tissue) to the surface
of intact endothelial cells appears to be an early event in
the development of atherosclerotic lesions [Hajjar DP and
Nicholson AC, 1995]. Investigators have determined that
monocyte binding to the endothelium of animals fed a high-cholesterol
diet is preceded by expression of the vascular cell adhesion
molecule (VCAM) and that a lipid is ultimately responsible
for activating the gene for VCAM [Gimbrone MA, Jr. Cybulsky
MI, et al. Anne New York Acad Sci. 1995:748:122].
The expression of VCAM on the endothelium can
be altered by abrupt changes in the direction and force of
local blood flow at atherosclerotic lesion-prone sites in
the circulatory system [Gimbrone MA and Cybulsky MI, 1995].
Specifically, a shear-stress responsive element, identified
in the regulatory region of several genes, has been show to
promote the expression of adhesion molecules as well as other
molecular factors that participate in atherogenesis.
One mechanism by which abnormal shear forces on the surface
of an endothelial cell can induce the expression of genes
that contribute to the development of atherosclerosis may
involve certain transcription factors (proteins that bind
to regulatory regions of genes) that are produced in response
to shear stress [Davies PF, Tripathi SC. Circulation Research.
1993;72:239. Hajjar DP and Nicholson AC, 1995].
 After
adhesion, monocytes insinuate themselves between the tight
junctions of the endothelial cells and enter the subendothelial
space [Hajjar DP and Nicholson AC, 1995].
Immune mechanisms also appear to play a role
in atherogenesis [Ip JH, et al, 1994. Hajjar DP and Nicholson
AC, 1995]. In particular, T-lymphocytes (cells responsible
for the cell-mediated immune response) have been found to
be present, albeit in small numbers, in both early fatty lesions
and in advanced fibrous lesions in humans. It has been
suggested that activation of T-lymphocytes during atherogenesis
may be similar to other immune responses in which T-cells
help to mobilize macrophages.
 After
monocytes have migrated beneath the endothelial layer into
the intima, they are transformed into a phagocytic state (macrophages)
in which they ingest modified lipids (primarily oxidized lipids)
[Hajjar DP and Nicholson AC, 1995]. As atherogenesis
progresses, these macrophages take on a "foamy"
appearance (thus their designation as "foam cells")
and become one of the primary components of the fatty streak.
The mechanisms by which macrophages accumulate
lipids within the intima and the possible role of T-lymphocytes
in this process are major areas of research.
|
Stroke Education
