Atherosclerosis: a bioengineer’s perspective

2/24/10

Cardiovascular disease (CVD)

• #1 cause of death in the United States• In 2006, claimed more lives than cancer, car

accidents, and HIV (AIDS) combined• About 25% of Americans have some form of CVD• 100% of people exhibit vessel stiffening which

correlates with risk of CVD americanheart.org

foodnetwork.com med.cornell.edu

Atherosclerosis

• What is it?

• Where does it occur?

Primarily in arteries

Risk Factors

• High Cholesterol• Hypertension• Diabetes• Smoking• Inactivity• Obesity

Detection?

• Atherosclerosis is typically asymptomatic!

• It is most often found after it manifests itself as a heart attack or stroke

• Measure of LDL within the blood as a predictor

• 20% of events occur in individuals with no major risk factors

Endothelial cell Monocyte Macrophage Foam cell Smooth muscle cell

Internal elastic lamina

Vessel lumen

1. Endothelial permeability

4. SMC migration2. Monocyte

adhesion and transmigration

Increased stiffness

3. Macrophage transformation into foam cells

The major cellular events in the progression of atherosclerosis

Histology of a normal artery

http://www.siumed.edu/~dking2/crr/cvguide.htm

The medial layer contributes most to the mechanical strength of an artery

Stresses in the vasculature

Effect of shear stress of endothelial cell orientation

flow

Hemodynamics within arterial lesions: A longstanding bioengineering problem

Malek AM et al (1999)

Flow pattern Arteriogram of a stroke patient Velocity map of flow

Streamlines at a carotid bifurcation

Lifeforcehospital.org

Young’s modulus: measuring stiffness

or

Young’s modulus of soft tissues

Modified from Levental, et al. Soft Matter 2007

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We can mimic blood vessel stiffness using gels

Monomer

Crosslinker

+

Polymer or gel

Endothelial cell Monocyte Macrophage Foam cell Smooth muscle cell

Internal elastic lamina

Vessel lumen

1. Endothelial permeability

4. SMC migration2. Monocyte

adhesion and transmigration

Increased stiffness

3. Macrophage transformation into foam cells

The major cellular events in the progression of atherosclerosis

The next two days…

• Polymer lab– Learn to make gels of varying stiffness– Explore the viscoelastic properties of gels

• Blood vessel lab– Learn how blood vessels control the continuous

flow of blood– Explore how the mechanical properties of blood

vessels affect blood flow