Unit 6 - Blood Lipoproteins Flashcards Preview

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Flashcards in Unit 6 - Blood Lipoproteins Deck (46)
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what does esterification of cholesterol maintain?

maintains cholesterol gradient to allow further uptake of cholesterol from peripheral tissues to HDL
-as HDL picks it up, CE converts from discoid to cholesterol-poor HDL3, then CE-rich HDL2 that carries CE to liver


what is Tangier disease?

deficiency in ABCA1 that causes absence of HDL particles b/c of degradation of lipid-free apo A1


what does hepatic lipase do?

degrades TAG and PL
-also participates in conversion of HDL2 to HDL3


relationship between macrophages and scavengers

macrophages have high levels of scavenger receptor activity (SR-A)
-bind range of ligands to cause endocytosis of modified LDL where lipid or apo B have undergone oxidative damage
-scavenger receptor not regulated by intracellular cholesterol concentration
-macrophages consume excess oxidized LDL to become foam cells, which participate in plaque formation


how does plaque formation start?

1. in response to endothelial injury from oxidized LDL, monocytes adhere to endothelial cells, move to intima, and convert to macrophages
2. macrophages consume excess oxLDL to become foam cells
3. foam cells accumulate, releasing growth factors and cytokines to stimulate migration of smooth muscle cells from media to intima; SMCs grow, make collagen, take up lipid, and may become foam cells
4. low affinity, nonspecific, and nonregulated scavenger receptors take up oxLDL
5. high affinity receptors specific for LDL are downregulated when the cell has enough cholesterol


what causes oxidation of LDL? what inhibits it?

+ superoxide, nitric oxide, hydrogen peroxide, other oxidants
- vit E/C, beta-carotene, other antioxidants


LDL receptor
-what it recognizes
-its function

recognizes apo B-100, E
-expressed in most cells, and regulates entry of CE into cells
-tight control mechanisms alter expression
-involved in LDL uptake
-deficiency causes familial hypercholesterolemia


LDLR-related PRO (LRP)
-what it recognizes
-its function

recognizes apo E, but not apo B-100
-metabolism of apo E containing LPs (CM and VLDL remnants), but doesn't recognize LDL


PCSK9 (proprotein convertase subtilisin/Kexin 9)
-what it recognizes
-its function

modulates LDL receptor
-upregulation causes degradation of LDLR and elevated LDL
-downregulation is associated with lifelong decrease in LDL and lower CAD risk


scavenger receptor A
-what it recognizes
-its function

recognizes oxidized LDL
-macrophage uptake of oxLDL, but not regular LDL
-not suppressed by high cellular cholesterol, so subintimal macrophages accumulate cholesterol to become foam cells and form fatty streaks
-involved in early athersclerosis


scavenger receptor B
-what it recognizes
-its function

recognizes HDL by liver and steroid producing cells
-includes CD36 and SR-B1


how does atherosclerotic plaque buildup?

as plaque within blood vessel matures, a cap forms over expanding "roof" to partially occlude vascular lumen
-vascular smooth muscle cells migrate from media to subintimal space, and secrete plaque matrix materials and metaloproteases that thin fibrous cap
-thinning continues until cap ruptures, exposing contents to procoagulants in circulation, causing thrombus formation
-if thrombus completely occludes blood vessel lumen, acute MI occurs


what are the components of a standard fasting lipid panel?

total cholesterol: enzymatic (cholesterol esterase)
triglycerides: enzymatic (lipase)
HDL-C: direct after precipitation of apo-B
VLDL-C: estimated as TG/5
LDL-C: calculated by Friedewald formula
non-HDLC: TC - HDL-C

recommend fasting 12-14 hours to minimize postprandial hyperlipidemia


what is Friedewald formula? when is it not valid?

total cholesterol = LDL + HDL + VLDL
LDL = TC - [HDL + VLDL] = TC - [HDL + TG/5]

not valid if TG > 400 mg/dL


what is dyslipoproteinemia?

also dyslipidemia
-constitutes major risk factor for athersclerosis and CAD
-most common rarely cause symptoms or produce clinical signs present on exam, but need laboratory tests


what are optimal lipid values?

TC < 200
TG < 150
LDL < 100
HDL > 50 (female), > 40 (male)
non-HDL < 130
TC/HDL < 4 (reflects balance of transport of cholesterol to peripheral tissues with subsequent uptake in arterial walls, and reverse transport to liver)

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