BIOM30001 Lecture 7: 7 Lipids in health and disease 2
Atherosclerosis is the build up of lipid and growth of smooth muscle cells (SMCs)
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Plaque or ‘atheroma’ contains fatty material (mainly cholesterol), SMCs and connective
tissue
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An unstable plaque may detach, form a clot and block a vessel
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RCT is a possible explanation for the inverse relationship between HDL levels and
atherosclerosis, ie high HDL-cholesterol, low risk of atherosclerosis
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HDL picks up excess free cholesterol from artery walls (e.g. from foam cells =
macrophages in atherosclerosis), converts them to cholesteryl esters (CEs) and delivers
them to the liver for disposal as bile, via a receptor called SR-BI
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Cholesterol in HDL can also be exchanged for TAGs from LDL
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HDL produced in the blood stream from ApoA-I and some phospholipids (not produced in the
liver, and not made from LDL)
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HDL precursor is a disc of ApoA-1 and phospholipid - made in liver and intestine
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The disc transforms into a sphere (HDL3) when free cholesterol is esterified to CE by the
enzyme LCAT (lecithin cholesterol acyl transferase)
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The sphere grows (→HDL2) as more free cholesterol is picked up and esterified
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HDL2exchanges cholesteryl ester for TAG from LDL and VLDL under the action of protein CETP
(cholesteryl ester transfer protein)
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HDL finally interacts with membrane protein SR-B1 on the liver and transfers its cargo of CE to
the liver. The remaining ApoA-I can float off and form another particle
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LDL delivers the CE to hepatocytes via the LDL receptor
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Reverse cholesterol transport (RCT)
Free cholesterol leaves cells (e.g. macrophage) through ABCA1 to form the pre-HDL disc
(nascent cholesterol); ABCG1 mediates flow of free cholesterol to spherical HDL
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Cholesterol interacts with phospholipid that binds ApoA-I > LCAT converts it to a small
sphere > large sphere
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Production/metabolism of HDL
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sphere > large sphere
CETP causes exchange of CE for TAG between HDL2 and (V)LDL
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HDL sub-populations
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ApoA-I shown wrapped around
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Larger HDL particles are more protective
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High levels of α-1 HDL are a marker of protection from heart disease.
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Increased small HDL particles are associated with a deficiency in HDL maturation and increased
CVD risk
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Factors that affect blood levels of cholesteryl esters and
triacylglycerols
Factors that affect blood cholesterol (C)
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Document Summary
Rct is a possible explanation for the inverse relationship between hdl levels and atherosclerosis, ie high hdl-cholesterol, low risk of atherosclerosis. Atherosclerosis is the build up of lipid and growth of smooth muscle cells (smcs) Pla(cid:395)ue o(cid:396) (cid:858)athe(cid:396)o(cid:373)a(cid:859) (cid:272)o(cid:374)tai(cid:374)s fatty (cid:373)ate(cid:396)ial (cid:894)(cid:373)ai(cid:374)ly (cid:272)holeste(cid:396)ol(cid:895), smcs a(cid:374)d (cid:272)o(cid:374)(cid:374)e(cid:272)ti(cid:448)e tissue. An unstable plaque may detach, form a clot and block a vessel. Hdl produced in the blood stream from apoa-i and some phospholipids (not produced in the liver, and not made from ldl) Hdl picks up excess free cholesterol from artery walls (e. g. from foam cells = macrophages in atherosclerosis), converts them to cholesteryl esters (ces) and delivers them to the liver for disposal as bile, via a receptor called sr-bi. Cholesterol in hdl can also be exchanged for tags from ldl. Hdl precursor is a disc of apoa-1 and phospholipid - made in liver and intestine.
