CVD 1

Question 1

1. What is the prevelence of death due to CvD in the U.S.?

Answer 1

1 in every 2.9 deaths is due to cardiovascular disease

Question 2

1. As a systemic disease, most coronary artery disease patients also have…

Answer 2

concomitant peripheral or cerebrovascular disease or cerebrovascular disease; if a patient has one plaque its likely they have plaques elsewhere although plaques are not homogenous.

Question 3

1. Name the risk factors for atherosclerosis (6 main)

Answer 3

age (men>45 women>55), DM, family hx (1st deg relative male <65), hypertension, cigarette smoking, dyslipidemia

Question 4

1. How is age such an important factor in development of CVD?

Answer 4

age is important because it measures the time the patient has been exposed to risk factors, also natural aging processes cause changes in the vasculature

Question 5

1. How do factors like cig. Smoke , dyslipidemia or family hx. Contribute to disease?

Answer 5

chemicals in smoke can lead to damage to b.v.; dyslipidemia adds to the pool of cholesterol and lipids that contribute to plaques and genetic factors can effect the way people metabolize lipids

Question 6

2. What are characteristics of a “normal” artery? (describe normal 3 layers)

Answer 6

endothelium resting on a thin basal lamina, subendothelial space containing thin elastic and collagenous fibers, longitudinally oriented smooth muscle cells

Question 7

2. Name two factors that are produce by endothelial cells that contribute to the normal functioning of the b.v.

Answer 7

normal levels of NO (promotes constitutive vasodilation), normal t-PA: PAI-1 promotes fibrinolysis (prevents platelet adhesion); damaged endothelium can attrach leukocytes to adhear and migrate into vessel wall

Question 8

2. Name the enzyme that produces constitutive NO.

Answer 8

constitutive membrane-associated Nosynthase (eNOS), note higher levels of shear stress induce higher levels of NO (O2+ L-arginine is converted to NO and L-citrulline)

Question 9

2. What is meant by the expression NO supply is “quenched”?

Answer 9

supply of NO reacts with excess oxidative free radicals which converts NO to oxidative compounds

Question 10

2. Describe the steps in atherosclerosis where lipoproteins eventually cause an inflammatory response.

Answer 10

lipoprotein gets in the subendothelial cells and are modified (glycosolation and oxidation) and oxidized LDL causes inflammatory response via MCP-1 and M-CSF factors

Question 11

2. What immune cells mediate the inflammatory response during atherosclerosis?

Answer 11

oxidation of LDL causes expression of monocyte scavenger receptors which enter into the subendothelial space and eat debris, causing a coalescence of cholesterol inside the macrophage, creating a foam cell which further produces IL, and proteases which activate SM migration

Question 12

2. How is atherothrombosis part of the formation of a plaque?

Answer 12

occuring concurrently with the addition of lipoproteins, factors produced by endothelium like t-PA keep platelets from sticking but damage or sloughing of endothelial cells can cause platelets to stick , clot formation causes release of factors that activate SM cells

Question 13

2. Name the critical cytoine-regulated adhesion molecule that binds mononuclear leukocytes and where/why is it expressed.

Answer 13

vascular cell adhensin molecule (VCAM-1) is expressed over damaged endothelium (fatty streaks due to athrogenic diet) (note atherogenic diet rapidly induces VCAM-1 in rabbit aortic endothelium)

Question 14

2. Once adheard to the vascular wall, monocytes respond to this chemotactic stimuli by penetrating from the endothelial surface into the arterial intima

Answer 14

monocyte chemoatractant protein-1, produced by endothelial and smooth muscle cells (even in the excess of LDL, MCP-1 seems key in causing development of atherosclerosis)

Question 15

2. An activated macrophage expresses this, it leads to the formation of a foam cell.

Answer 15

expression of scavenger receptors that internalized modified LDL promotes foam cell formation

Question 16

2. Name the factors that promote mitosis of macrophages in a atherosclerotic plaque.

Answer 16

macrophage colony-stimulating factor, produced by endothelial and smooth muscle cells

Question 17

2. When a fatty streak is present, is the endothelium normally intact?

Answer 17

yes, the tunica meida may show some disarray due to the beginnings of smooth muscle migration

Question 18

2. What is the key characteristic of the vessel that denotes a plaque has formed.

Answer 18

discontinous endothelium with the formation of a fibrous cap