1. Atherosclerosis: a bioengineer’s perspective
2/24/10

2. 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

3. Atherosclerosis
What is it?
Where does it occur?
Primarily in arteries

4. Risk Factors High Cholesterol Hypertension Diabetes Smoking Inactivity
Obesity

5. 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

6. The major cellular events in the progression of atherosclerosis
Endothelial cell
Monocyte
Macrophage
Foam cell
Smooth muscle cell
Internal elastic lamina
Vessel lumen
1. Endothelial permeability
4. SMC migration
2. Monocyte adhesion and transmigration
Increased stiffness
3. Macrophage transformation into foam cells

7. Histology of a normal artery
The medial layer contributes most to the mechanical strength of an artery

8. Stresses in the vasculature

9. Effect of shear stress of endothelial cell orientation
flow

10. Hemodynamics within arterial lesions: A longstanding bioengineering problem
Flow pattern
Arteriogram of a stroke patient
Velocity map of flow
Malek AM et al (1999)

11. Streamlines at a carotid bifurcation
Lifeforcehospital.org

12. Young’s modulus: measuring stiffnessor

13. Young’s modulus of soft tissues
Atherosclerotic artery
Normal liver
Normal artery
Fat
Mammary gland
Premalignant breast
Breast tumor
Lymph node
Brain
100
1000
10000
Young’s Modulus (Pa)
Modified from Levental, et al. Soft Matter 2007

14. We can mimic blood vessel stiffness using gels
Monomer
% Bis
Young’s Modulus (Pa)
0.05
1800
0.1
2500
0.2
6000
0.3
8000 +
Polymer or gel
Crosslinker

15. The major cellular events in the progression of atherosclerosis
Endothelial cell
Monocyte
Macrophage
Foam cell
Smooth muscle cell
Internal elastic lamina
Vessel lumen
1. Endothelial permeability
4. SMC migration
2. Monocyte adhesion and transmigration
Increased stiffness
3. Macrophage transformation into foam cells

16. The next two days… Polymer lab Blood vessel 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