Atherosclerosis
Mike Clark, M.D.
Terms
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Arteriosclerosis – hardening of the arteries
Atherosclerosis – a form of arteriosclerosis
Venosclerosis
Arteriolosclerosis
Step One of Atherosclerosis
Endothelium injured
The tunica interna is injured in some way by
bloodborne chemicals, hypertension,
components of cigarette smoke or viral or
bacterial infections. Almost any type of
chronic infection – including periodontal
disease can cause the damage.
Step Two of Atherosclerosis
Lipids accumulate and oxidize in the tunica intima
Injured endothelial cells release chemotactic agents and
growth factors (VEGF) and begin to modify lipids picked
up from blood, in particular LDL, that delivers cholesterol
to tissues. The accumulated LDL is oxidized as a result of
the endothelial inflammation. This damages neighboring
endothelial and tunica interna cells – and acts as a
chemotactic agent, attracting macrophages. Some of
these macrophages become so engorged with LDL that
they are transformed into lipid-laden cells termed “foam
cells.” The accumulation of these foam cells in the local
area forms a fatty streak – the first sign of the of
atheroma development.
Step Three of Atherosclerosis
Smooth muscle cells migrate and proliferate and a
fibrous cap forms
Smooth muscle cells migrate from the tunica media
and deposit collagen and elastic fibers in the
tunica intima – thus producing fibrous lesions
with a cord of dead and dying foam cells – termed
a fibrous or atherosclerotic plague. At first the
growing plaque causes expansion of the vessel
wall – but eventually the plague causes narrowing
of the vessel lumen.
Step Four of Atherosclerosis
The Plague becomes unstable
As the plaque continues to enlarge, the cells at its
center die. Calcium is deposited, and collagen fiber
production by smooth muscle cells declines. Now
called a complicated plaque – it constricts the
vessel wall and caused the arterial walls to fray and
ulcerate, conditions that encourage blood sludging
and backup, platelet adhesion, and thrombus
formation. The vessels increased rigidity leads to
hypertension. Together these events increase the
risk of myocardial infarction, strokes, and
aneurysms, that are responsible for pain (angina)
that occurs when heart muscle becomes ischemic.
Damaged Endothelial Cells
• 1. Produce less Nitric Oxide – a local vasodilator
and inhibitor of platelet aggregation
• 2. Produce less Prostacyclin (PGI2) – an inhibitor
of platelet aggregation
• 3. Produce less thrombomodulin – inhibits
coagulation
• 4. Produces less heparin-like molecules
• 5. Produce more von Willebrand factor and tissue
thromboplastin – which promote coagulation.
Figure UN 19.1