The Pathophysiology

of Atherosclerosis
By: VSS

Definition of Atherosclerosis
Atherosclerosis

can be described as the

hardening and narrowing of the arteries that
occur due to a build up of atherosclerotic
plaque in the arterial wall. This plaque usually
contains white blood cells, smooth muscle
cells, cholesterol, lipids, calcium, collagen and
fibrin and over time increases in size.

The

plaque eventually encroaches on the

lumen of these vessels

How is an
atherosclerotic plaque
formed?

The tissue layers of an artery

How are plaques formed?

An initial injury or dysfunction of the vascular

endothelium is believed to trigger plaque formation or
atherogenesis
Injury could be caused by
Elevated levels of cholesterol and triglycerides in the
blood
High blood pressure
Cigarette smoking
Injury causes increased permeability of the endothelium
to low density lipoproteins (LDLs)

How plaques are formed

LDLs

penetrate endothelium and deposit in

the arterial intima where they become
oxidized by reactive oxygen species released
by the dysfunctional endothelial cells

Oxidized

LDLs activate endothelial cells to

produce adhesion molecules

How plaques are formed

The adhesion molecules bind

to leukocytes namely,
monocytes and T-helper
cells.

Once bound to the adhesion

molecules, the leukocytes
enter the intima where the
monocytes differentiate into
macrophages.

The macrophages take up

oxidized LDLs and become
foam cells which form a
fatty streak in the artery wall.

How plaques are formed

The foam cells release

chemokines to attract more
macrophages

They also release IGF-1

which promotes Smooth
muscle cell (SMC) migration
from the tunica media into
the intima, and their
subsequent proliferation

The increased proliferation of

SMC cells leads to increased
synthesis of collagen which
causes hardening of the
plaque

How plaques are formed

T-Helper

cells produce IFN which activate

endothelial cells to produce more adhesion
molecules and bind more white blood cells to
produce even more foam cells

How plaques are formed

When foam cells die, they

release their lipid contents
into the plaque which drives
the growth of the plaque
Foam cells also release
proinflammatory cytokines
and reactive oxygen species
which both increase
inflammation in the area
Pressure increases in the
plaque which can cause the
plaque to rupture and lead to
thrombus formation

Thrombus formation
If

the plaque ruptures, coagulation occurs to

prevent the plaque from spilling its contents
into the lumen of the vessel
The thrombus formed can impede blood flow
leading to ischemia

Summary

References
https://www.youtube.com/watch?v=R6QTiBf

zULE
Clinical Medicine Kumar and Clarke