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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
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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
The major cellular events in the progression of atherosclerosis Monocyte Endothelial cell Foam cell Macrophage Smooth muscle cell Vessel lumen 4. SMC migration 2. Monocyte adhesion and transmigration 1. Endothelial permeability Increased stiffness Internal elastic lamina 3. Macrophage transformation into foam cells
Histology of a normal artery The medial layer contributes most to the mechanical strength of an artery http://www.siumed.edu/~dking2/crr/cvguide.htm
flow Effect of shear stress of endothelial cell orientation
Hemodynamics within arterial lesions: A longstanding bioengineering problem Velocity map of flow Arteriogram of a stroke patient Flow pattern Malek AM et al (1999)
Streamlines at a carotid bifurcation Lifeforcehospital.org
Young’s modulus of soft tissues 10000 1000 Young’s Modulus (Pa) Atherosclerotic artery Premalignant breast Mammary gland 100 Breast tumor Lymph node Normal liver Normal artery Brain Fat Modified from Levental, et al. Soft Matter 2007
We can mimic blood vessel stiffness using gels Monomer + Polymer or gel Crosslinker
The major cellular events in the progression of atherosclerosis Monocyte Endothelial cell Foam cell Macrophage Smooth muscle cell Vessel lumen 4. SMC migration 2. Monocyte adhesion and transmigration 1. Endothelial permeability Increased stiffness Internal elastic lamina 3. Macrophage transformation into foam cells
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