Lipoprotein & Atherogenesis Flashcards
what are the components of lipoprotein?
what are the major lipoproteins?
phospholipid, cholesterol, apoprotein, tryglyceride & cholesteryl esters
HDL, LDL, IDL, VLDL & chylomicrons
What type of lipoprotein considered to be bad?
Why?
LDL
because it has the highest % cholesterol of its components
What major protein is LDL made of?
ApoB100
Protein ApoB48 are exclusively in what lipoprotein?
chylomicrons
What type of protein only found in HDL?
ApoD
ApoE
What type of lipoproteins is this protein in?
proteins that help inhibiting the developmen of atherosclerosis
all lipoproteins except LDL
What are the primary proteins in HDL?
ApoA I & II
What does ApoA I & II do?
activate LCAT, which convert free cholesterol into cholesteryl esters
What are the endothelium-derived vasodilator?
vasoconstrictor?
Ach, shear stress, serotonin & thrombin
thrombin, angiotensin II & epinephrine
thrombosis
what does it cause?
the development of blood clot inside the vessels
obstructing the blood flow
Mechanism against the thrombosis
inactivation of thrombin by antithrombin III
Inactivation of factor V & VIII by protein C+ S
______ VII & tissue complex
______ VIIa by TFPI & complex Xa
lysis of fibrin by plasminogen activator
Inactivation of platelets activation
what are substances that endothelial-derived vasodilator influence?
NO
prostacyclin
EDHF
How does prostacyclin inhibit the platelet activation?
increase lvl of cAMP
increase blood flow & minimize contact btw thrombogenic factors
How does cell uptake the cholesterol?
ApoB100 binds to LDL-R and undergo endocytosis
thrombus
the blood clot
What factors do protein C+S inhibit in mechanism against thrombosis?
Factor V + VIII
What hormone can act as vasodilator if there is damage to vessel?
serotonin
atherogenesis
the formation of abnormal fat deposits within the arterial walls of blood vessels
What are the causes of atherogenesis?
the endothelial or vascular smooth muscular cells dysfunction
What cause the endothelial dysfunction?
chemical irritants or hemodynamic stress
What is the effect of increase lvl of cAMP to platelets?
inhibit platelet aggregations & adhesion
What are two vasodilators that help against thrombosis?
NO
prostacyclin
What from what protein that Apo48 is derived from?
ApoB100
hemodynamic stress
the frictional force acting endothelial cells as result of blood flow
What are the results of endothelial dysfunction?
inflammation cytokines
lipoprotein entry & modification
how does the foam cell formation occur?
unregulated uptake of modified LDL
& leukocyte recruitment
What are two products that both lipoprotein modification & inflammatory cytokines both produce?
chemokines & leukocytes adhesion molecules
what happen to endothelial cells when they are inflammed?
antithrombotic molecules decrease
vasodilators decrease
permeability to large molecules increase
inflammatory cytokines increase
leukocytes molecules increase
What happen when smooth muscular cells migrate & proliferate in subendothelial space?
fibrous plague formation
What are two substances that signal leukocyte recruitment?
chemokines
leukocyte adhesion molecules
What happens to smooth muscular cells when they are inflammed?
inflammatory cytokines increase
migration and proliferation in the endothelial lining
extracellular synthesis increases
The protein that is in all lipoproteins except LDL
What does it do?
ApoE
help inhibiting atherosclerosis development
Events in atherogenesis
1) LDL particles pass into sub-endothelial cells
2) LDL is oxidized by ROS and oxidizing enzymes secreted by macrophages
3) monocytes are attracted to site by chemo-attractant molecules
4) Monocytes differentiate into macrophages & secrete inflammatory cytokines
5) secreted inflammatory cytokines & PDGF activate smooth muscle cells to migrate & proliferate in sub-endothelial space
What does oxidize LDL?
phagocytes secreted by macrophages & ROS (reactive oxygen species)
When LDL is oxidized, what will it turn into?
foam cell
After monocytes differentiate into macrophages, what do they secrete?
phagocytes that oxidized LDL
inflammatory cytokines
What is the key step in atherogenesis event?
when LDL is oxidized to become foam cell
How does LPL particle enter the sub-endothelial space?
Protein ApoB100 binds to negative charge of proteoglycans in matrix
Where does unstable plague will rupture?
along the border with normal tissue where the hemodynamic stress is greatest
What signals the VSMC to migrate and proliferate into sub-endothelial space?
inflammatory cytokines
What does the VSMC do to streghthen the fibrous plague?
excrete more matrix proteins
When does the fibrous plague begin?
when VSMC begin migrate and proliferate in sub-endothelial space
