Flashcards in CVD 1 Deck (18):
1. What is the prevelence of death due to CvD in the U.S.?
1 in every 2.9 deaths is due to cardiovascular disease
1. As a systemic disease, most coronary artery disease patients also have…
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.
1. Name the risk factors for atherosclerosis (6 main)
age (men>45 women>55), DM, family hx (1st deg relative male <65), hypertension, cigarette smoking, dyslipidemia
1. How is age such an important factor in development of CVD?
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
1. How do factors like cig. Smoke , dyslipidemia or family hx. Contribute to disease?
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
2. What are characteristics of a "normal" artery? (describe normal 3 layers)
endothelium resting on a thin basal lamina, subendothelial space containing thin elastic and collagenous fibers, longitudinally oriented smooth muscle cells
2. Name two factors that are produce by endothelial cells that contribute to the normal functioning of the b.v.
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
2. Name the enzyme that produces constitutive NO.
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)
2. What is meant by the expression NO supply is "quenched"?
supply of NO reacts with excess oxidative free radicals which converts NO to oxidative compounds
2. Describe the steps in atherosclerosis where lipoproteins eventually cause an inflammatory response.
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
2. What immune cells mediate the inflammatory response during atherosclerosis?
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
2. How is atherothrombosis part of the formation of a plaque?
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
2. Name the critical cytoine-regulated adhesion molecule that binds mononuclear leukocytes and where/why is it expressed.
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)
2. Once adheard to the vascular wall, monocytes respond to this chemotactic stimuli by penetrating from the endothelial surface into the arterial intima
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)
2. An activated macrophage expresses this, it leads to the formation of a foam cell.
expression of scavenger receptors that internalized modified LDL promotes foam cell formation
2. Name the factors that promote mitosis of macrophages in a atherosclerotic plaque.
macrophage colony-stimulating factor, produced by endothelial and smooth muscle cells
2. When a fatty streak is present, is the endothelium normally intact?
yes, the tunica meida may show some disarray due to the beginnings of smooth muscle migration