Beruflich Dokumente
Kultur Dokumente
LIPOPROTEINBY&
Dr.Liniyanti D.Oswari, MNS,
DYSLIPIDEMIA
MSc.
Learning Objectives
Lipoproteins
Lipoproteins
Chylomicrons
VLDL Very low density lipoprotein
IDL Intermediate density
lipoprotein
LDL Low density lipoprotein
HDL High density lipoprotein
Lipoproteins
Distinguished by size
and density
Each contains
different kinds and
amounts of lipids and
proteins
Lipoproteins
Class
Size (nm)
Lipids
Major
Apoproteins
Chylomicra
100-500
Dietary TG
B-48,C-II,E
VLDL
30-80
Endogenous
TG
B-100,C-II,E
IDL
25-50
B-100, E
LDL
18-28
CEs
B-100
HDL
5-15
CEs
A,C-II,E
Lp (a)
25-30
CEs
B-100 &
glycoproteins
VLDL
IDL
Cholesterol
22
35
47
19
Triglyceride
82
52
20
Phospholipi
d
18
20
23
28
Lipid
LDL HDL
Functions of Chylomicrons
Chylomicron remnants
Taken up by liver
Contents reused or recycled
Liver
Cholest
AA
FA
P,
glycerol
Vessel
wall
Exogenous
Intestine
(~300700 mg/day)
Biliary
cholesterol
Fecal bile
acids
and neutral
sterols
~700 mg/day
(~1000 mg/day)
Liver
Synthesis
(~800 mg/day)
Extrahepatic
tissues
Endogenous
Adapted from Champe PC, Harvey RA. Biochemistry. 2nd ed. Philadelphia: Lippincott Raven, 1994; Glew
RH. In Textbook of Biochemistry with Clinical Correlations. 5th ed. New York: Wiley-Liss, 2002:728-777;
Ginsberg HN, Goldberg IJ. In Harrisons Principles of Internal Medicine. 14th ed. New York: McGraw-Hill,
1998:2138-2149; Shepherd J Eur Heart J Suppl 2001;3(suppl E):E2-E5; Hopfer U. In Textbook of
Biochemistry with Clinical Correlations. 5th ed. New York: Wiley-Liss, 2002:1082-1150.
1000 mg
Inhibitors
Resins
Plant stanols
NPC1L1
(Ezetimibe)
Very-Low-Density
Lipoproteins (VLDL)
Made by liver
Contains large amounts of
triglyceride
Delivers fatty acids to cells
More dense than chylomicrons
A bit more protein (8%)
3
1
2
4
Intermediate-Density
Lipoproteins (IDL)
Low-Density Lipoproteins
(LDL)
Protein (21%)
Cell membranes
Hormone production
ApoB-100
Binds to specific LDL receptor
LDL receptors
Increase LDL
SFAs
Trans fatty acids
High cholesterol
intake
Lifestyle factors
Genetics
Decrease LDL
Mechanism of Atherogenic
Dyslipidemia
Insulin resistance
increased NEFA
and glucose flux to
liver
Increased
VLDL
IR impairs
LDLR
Insulin
resistance and
decreased apoB degradation
Insulin
resistance
and
decreased
LPL
FCHL
DM II
Metabolic
syndrome
Direct Association
Indirect
Association
Inverse relationship
with HDL
Marker for
atherogenic TG
remnant
accumulation
Insulin resistance
High-Density Lipoproteins
(HDL)
Protein (50%)
HDL Metabolism
Antiinflammatory
Anti-thrombotic
Modulation of
endothelial function
HDL-C
Cholesterol
acceptor
Cholesterylester
donor
Reverse
Cholesterol
Transport (RCT)
Dyslipidemia Characteristics
Elevated triglycerides
Post-prandial lipemia
Small dense LDL (type B)
Elevated LDL
Low HDL cholesterol
Elevated Total
Cholesterol
Mechanisms Relating
Insulin Resistance and
Dyslipidemia
Fat Cells
Liver
FFA
IR
Insulin
CE
TG
VLDL (CETP) HDL
(hepatic lipase)
Apo B
TG
VLDL
Apo A-1
CE (CETP) TG
LDL
SD
LDL
(lipoprotein
or
hepatic lipase)
Kidney
Dyslipidemia in
Diabetes
Increased
Decreased
Apo B
HDL
Triglycerides
Apo A-I
VLDL
LDL and
Small Dense
LDL
Insulin Resistance:
Associated Conditions
Low HDL-cholesterol
Low HDL-cholesterol
Low HDL-cholesterol
Low HDL-cholesterol
Increased catabolism of small dense
HDL
Low HDL cholesterol by both content
and # particles
CETP
inhibitors
High triglycerides
Post-prandial
lipemia
Small dense LDL
(type B)
Low HDL
cholesterol
Fibrate
Niacin
Statin
CETP
ABCA-1
Current Classifications
Tangier Disease
Cardiovascular disease
(CVD)
Cardio = heart
Vascular = blood vessels
Lipoproteins and
cardiovascular disease (CVD)
LDL is positively associated with
risk
CVD
Atherosclerosis Is an Inflammatory
Disease
L-Selectin,
Integrins
VCAMLDLE-Selectin,
1,
P-Selectin
ICAM-1
Monocyt
e
MCP-1
OxLDL
Intima
M-CSF
Other
inflammato
ry triggers
Macrophage
Activation &
Division
Media
Libby et al. Circulation 2002;105:1135-1143.
Atherosclerosis Is an Inflammatory
Disease
Oxidation of low-density lipoprotein (LDL)
initiates the atherosclerotic process in the
vessel wall by acting as a potent stimulus for
the induction of inflammatory gene products in
vascular endothelial cells. By activating the
nuclear factor B (NFB) transcription factor,
oxidized LDL (oxLDL) stimulates increased
expression of cellular adhesion molecules.
There are several different types of adhesion
molecules with specific functions in the
endothelialleukocyte interaction: The selectins
tether and trap monocytes and other
leukocytes. Importantly, vascular cell adhesion
molecules (VCAMs) and intercellular adhesion
Atherosclerosis Is an Inflammatory
Disease
ICAM-1
Selectins, HSPs,
etc.
Endothelium
and other
cells
IL-6
Messenger
Cytokine
CRP
SAA
Liver
Circulation
HSPs=heat shock proteins; SAA=serum amyloid-A.
Adapted from Libby and Ridker. Circulation. 1999;100:1148-1150.
Desirable Blood
Cholesterol
Physical
inactivity
Excessive
food intake
Stress
Smoking
Obesity
Hypertension
Risk factor
modificatio
n
Diabetes
Dyslipidaemia
Atherosclerosis
Chronic
heart failure
Atherosclerosis
Arrhythmia
Definition:(NCEP)
National Cholesterol Education Program (2001)
At least 3 of
Abdominal obesity: waist circumference > 102 cm (M)
> 88 cm (F)
Hypertriglyceridemia
Central
obesity
Insulin
Resistan
ce
Type 2
Diabetes
Dyslipidemi
a
Hypertensio
n
Environmental factor
Genetic variation
Abdominal
Adipokines obesity
Adipocyte
Cytokines
Monocyte/
macrophag
Inflammatory markers
Insulin resistance
Tg
Metabolic syndrome
HDL
BP
Atherosclerosis
Plaque rupture/thrombosis
Cardiovascular events
Treatment
Treatment
Medications
Procedures
Angioplasty
CABG
Drugs
Treatment
Nutrition Therapy
Polyunsaturated fat
Up to 10% of total calories
Monounsaturated fat
Up to 20% of total calories
Total fat
25-30% of total calories
Carbohydrates
50-60% of total calories
Fiber
20-30 grams/day
Protein
Approx. 15% of total calories
Total calories
Balance energy intake and
expenditure to maintain
desirable body weight/
prevent weight gain
*Avoid Trans Fats.
* Increase Intake of Omega -3 essential Fatty Acids
Medical Treatments
Coronary
Angioplasty
Coronary Bypass
Surgery (CABG)
Diet Supplements
Soy
Garlic
Cholesterol-lowering Margarines
Benecol and Take Control containing plant sterols and stanols