Lipoprotein Lecture (Lecture 6)

Question 1

What is coronary artery disease?

Answer 1

Leading cause of natural death in the world.; correlated with the levels of plasma cholesterol and d triacylglycerol containing lipoprotein particles

Question 2

Steady-state levels of lipoprotein in the ciculation can be influenced by what?

Answer 2

genetic factors, diet, obesity, and other factors

Question 3

What are hyperlipidemias?

Answer 3

complex group of diseases that can be designated either primary or secondary, depending on their causes

Question 4

What are primary hyperlipidemias?

Answer 4

Can result from a single inherited gene defect, or more commonly, are caused by a combination of genetic and environmentals factors

Question 5

What are secondary hyperlipidemias?

Answer 5

the result of a metabolic disorder, such as diabetes mellitus, obesity, hypothyroidism, or primary biliary cirrhosis

Question 6

Therapeutic strategies for treating hyperlipidemia

Answer 6

dietary intervention, regimen of drugs

Question 7

Hypertriglyceridemia

Answer 7

defined as total plasma triglycerides in the fasting state in excess of 150 mg/dl; due to an abnormally high quantitiy of chylomicrons, VLDL, or both

Question 8

Connection between hypertriglyceridemia and cardiovascular disease

Answer 8

hypertriglyceridemia increases a person’s risk for cardiovascular disease (nature of pathogenic lipoprotein is unclear)

Question 9

Major risk of sever hypertriglyceridemia

Answer 9

pancreatitis ; may also have eruptive and tuberous xanthomas

Question 10

Familial combined hyperbetalipoproteinemia (Type IIB)

Answer 10

defects in synthesis, processing or function of LDL receptors

Question 11

Inheritane pattern of familial combined hyperlipoproteinemia (type 2B)?

Answer 11

autosomal dominant with variable penetrance, with a population prevalence of 2%-5%

Question 12

Defining lipoprotein abnormalitis with familial combined hyperlipoproteinemia?

Answer 12

increased VLDL and LDL with depressed HDL

Question 13

How does familial combined hyperlipoproteinemia affect CETP activity?

Answer 13

increases CETP activity, and conseequently, rapid formation of both small LDL particles and small HDL particles

Question 14

Treatment for hypertriglyceridemia?

Answer 14

(1) life-style modification

2) drug treatment (statin, fish oil, fibrate, nicotinic acid

Question 15

How does Fibrate work?

Answer 15

activate PPARalpha transcription factors that lead to both increase lipoprotein lipase activity and an increased rate of fatt acid Beta-oxidation

Question 16

How does Nicotinic acid work?

Answer 16

works in part by activating niacin receptor 1 that inhibits lipolysis (the release of fatty acids from adipose tissue)

Question 17

Effect of statins?

Answer 17

reduce VLDL production

Question 18

Effect of fish oil?

Answer 18

Fish, which is omega-3 fatty acids, increases lipoprotein lipase activity

Question 19

Manifestations of primary hypercholesterolemia

Answer 19

tendon xanthomas, tuberous xanthomas, xanthelasma, atherosclerosis

Question 20

How does hypercholesterolemia lead to coronary artery disease?

Answer 20

Hypercholesterolemia –> atherosclerosis –> coronary artery disease

Question 21

What other health problems can hypercholesterolemia cause?

Answer 21

Buildup of excess cholesterol in other tissues

Question 22

Tendon xanthomas

Answer 22

cholesterol accuulates in tendons

Question 23

Xanthelasma

Answer 23

Yellowish cholesterol deposits under the skin of the eyelids

Question 24

Patients with hypercholesterolemia (no hypertriglyceridemia) have what kind of xanthomas?

Answer 24

tendon xanthomas, most often on the hands and feet

Question 25

Patients with combined hypercholesterolemia andhypertriglyceridemia, have what kind of xanthoas?

Answer 25

tubrous xanthomas, which form overjoints

Question 26

What is Lp(a)?

Answer 26

lipoprotein(a); a modest, independent risk factor for atherosclerotic cardiovascular disease (CVD) events, especially myocardial infaction; represent a circulating abnormal variant of LDL

Question 27

How does the formation of Lp(a) occur?

Answer 27

formation of Lp(a) occurs when apolipprotein a forms a disulfide bonded complex with the apoB-100 component of LDL

Question 28

Homozygous familial hypercholesterolemia?

Answer 28

two allels for a defective LDL-receptor (less often, patients are homozygous for loss-of-function mutations in apolipoprotein B-100)

Question 29

Heterozygous familial hypercholesterolemia

Answer 29

have a mutant allele for the LDL receptor about 5% of these patients have a mutant apolipoprotein B and about 2% have an overly active PCSK9 enzyme
(have about twice the usual LDL cholesterol)

Question 30

Apo A-1 deficiency

Answer 30

remember, A-I is a LCAT activator; if the HDL cannot get rid of cholesterol in this manner, its functional half-life is greatly shortened
- side note: Nonesterified cholesterol will be randomly deposited in excess, by the serum lipoprotein particles, for example in the cornea and in the vessels (corneal clouding)

Question 31

LCAT deficiency

Answer 31

may cause a complete deficiency (familial LCAT) or partial deficiency (fish-eye disease)

Question 32

characteristics of LCAT deficiency

Answer 32

reduced HDL and apoA1 levels, elevated TAGS, decreased LDL, early onset of corneal opacifications (more striking than those reported in Tangier disease or in ApoAI deficiency)

Question 33

What about heterozygous carriers of LCAT mutations?

Answer 33

clinically normal, and they frequently (but not always) present with low HDL-C levels

Question 34

Tangier Disease-Absence of ABCA1

Answer 34

autosomal recessive disorder due to loss-of-function mutations in the ABCA1

Question 35

Clinical presentation of Tangier disease

Answer 35

varies considerably. However, because cholesterol accumulates
in many issues throughout the body (tonsils, liver, spleen, Schwann cells), the major
clinical findings are enlarged orange tonsils,
hepatomegaly, splenomegaly, and occasionally mild corneal
opacification.

Question 36

Fibroblasts in a patient with Tangier Disease

Answer 36

Fibroblasts from patients

show a defective cholesterol and phospholipid efflux to apolipoproteins.

Question 37

How does exetimibe work?

Answer 37

inhibits absorption of cholesterol at the brush border membrane in the intestinal lumen and increase # of LDL receptors on liver (LDL decreases)

Question 38

How does Bile acid sequestrans work?

Answer 38

depleted the bile acid pool and disrupts the enterohepatic circulation of bile acids, thus, increasing the synthesis of bile acids from cholesterol