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Chapter 28: Lipids: Lipoproteins

An increase in which of the following apolipoproteins would most likely be associated with a reduced risk for the development of atherosclerosis?

A. apo(a)

B. apoA-I

C. apoC-I

D. apoC-II

E. apoE

Answer E: The cellular uptake of cholesterol from LDL occurs following the interaction of LDL with the LDL receptor (also called the apoB-100/apoE receptor). Both apoB-100, which is exclusively associated with LDL, and apoE are required for LDL receptor-mediated endocytosis of LDL. The importance of apoE in cholesterol uptake by LDL receptors has been demonstrated in transgenic mice lacking functional apoE genes. These mice develop severe atherosclerotic lesions at 10 weeks of age. Therefore, increased levels of apoE would be associated with a higher hepatic uptake of LDL, leading to reduced levels in the blood.

The hypercholesterolemia that is associated with familial hypercholesterolemia is due to which of the following?

A. abnormally elevated production of LDL

B. abnormally elevated production of VLDL by the liver

C. abnormally reduced production of HDL, resulting in a diminished capacity of reverse cholesterol transport

D. defective LDL receptors leading to reduced uptake of plasma LDL and IDL

E. defective remnant receptors on hepatic cells, leading to reduced uptake of chylomicron remnants

Answer D: Familial hypercholesterolemia, FH (type II hyperlipoproteinemia), is an autosomal dominant disorder that results from mutations affecting the structure and function of the cell-surface receptor that binds plasma LDL, removing them from the circulation. The defects in LDL-receptor (LDLR) interaction result in lifelong elevation of LDL-cholesterol in the blood. The resultant hypercholesterolemia leads to premature coronary artery disease and atherosclerotic plaque formation.

A 13-year-old girl presents with extensive eruptive xanthomas and hepatosplenomegaly. She does not have type 1 or type 2 diabetes as an analysis of circulating insulin and glucose levels indicates they are normal. Examination of plasma indicates that it quite milky, indicating a lipemia. Analysis of the lipid content of the plasma shows a massive accumulation of chylomicrons and triglycerides. The teenager is placed on a fat-free diet, which reduces the lipemia and all of the other clinical manifestations. A deficiency in which of the following apolipoproteins would account for the observed symptoms of this particular hyperlipoproteinemia?

A. apoA-I

B. apoA-IV

C. apoB-100

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