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

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

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

Stresses in the vasculature

Effect of shear stress of endothelial cell orientation flow

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

Streamlines at a carotid bifurcation Lifeforcehospital.org

Young’s modulus: measuring stiffness or

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

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

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

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