Lipoprotein Lecture (Lecture 6) Flashcards Preview

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Flashcards in Lipoprotein Lecture (Lecture 6) Deck (38):
1

What is coronary artery disease?

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

2

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

genetic factors, diet, obesity, and other factors

3

What are hyperlipidemias?

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

4

What are primary hyperlipidemias?

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

5

What are secondary hyperlipidemias?

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

6

Therapeutic strategies for treating hyperlipidemia

dietary intervention, regimen of drugs

7

Hypertriglyceridemia

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

8

Connection between hypertriglyceridemia and cardiovascular disease

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

9

Major risk of sever hypertriglyceridemia

pancreatitis ; may also have eruptive and tuberous xanthomas

10

Familial combined hyperbetalipoproteinemia (Type IIB)

defects in synthesis, processing or function of LDL receptors

11

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

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

12

Defining lipoprotein abnormalitis with familial combined hyperlipoproteinemia?

increased VLDL and LDL with depressed HDL

13

How does familial combined hyperlipoproteinemia affect CETP activity?

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

14

Treatment for hypertriglyceridemia?

(1) life-style modification
(2) drug treatment (statin, fish oil, fibrate, nicotinic acid)

15

How does Fibrate work?

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

16

How does Nicotinic acid work?

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

17

Effect of statins?

reduce VLDL production

18

Effect of fish oil?

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

19

Manifestations of primary hypercholesterolemia

tendon xanthomas, tuberous xanthomas, xanthelasma, atherosclerosis

20

How does hypercholesterolemia lead to coronary artery disease?

Hypercholesterolemia --> atherosclerosis --> coronary artery disease

21

What other health problems can hypercholesterolemia cause?

Buildup of excess cholesterol in other tissues

22

Tendon xanthomas

cholesterol accuulates in tendons

23

Xanthelasma

Yellowish cholesterol deposits under the skin of the eyelids

24

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

tendon xanthomas, most often on the hands and feet

25

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

tubrous xanthomas, which form overjoints

26

What is Lp(a)?

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

27

How does the formation of Lp(a) occur?

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

28

Homozygous familial hypercholesterolemia?

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

29

Heterozygous familial hypercholesterolemia

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)

30

Apo A-1 deficiency

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)

31

LCAT deficiency

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

32

characteristics of LCAT deficiency

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)

33

What about heterozygous carriers of LCAT mutations?

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

34

Tangier Disease-Absence of ABCA1

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

35

Clinical presentation of Tangier disease

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.

36

Fibroblasts in a patient with Tangier Disease

Fibroblasts from patients
show a defective cholesterol and phospholipid efflux to apolipoproteins.

37

How does exetimibe work?

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

38

How does Bile acid sequestrans work?

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