Flashcards in atherosclerosis Deck (27)
Things that can cause vascular damage leading to atherosclerosis
Turbulent blood flow
Chronic Inflammation, possibly some viruses, C. pneumonia
Cholesterol uptake transporters in the intestine
ER transporter of cholesterol
forms cholesterol esters from cholesterol acyl coa cholesterol transport protein.
What transcription factor regulates liver synthesis and export of cholesterol?
Liver X Receptor
What regulates Bile acid uptake in the ileum?
Ilial bile acit transporter
ileal bile acid binding protein
both are FXR regulated
Which HDL is taken back up by the liver?
What regulates cholestrol synthesis?
What regulates bile/cholesterol transport into the bile canaliculi?
What does LXR do
LXR stimulates bile acid synthesis,
by activating 7-alpha-hydroxylase
Increases ABCA1, ABCG1 activity, increased bile transport
Cholesterol Ester transfer protein,
Increasing cholesterol transfer into HDLs
Mutations in CETP increase atherosclerosis, and increasing activity increases Cholesterol clearance
What do insigs do?
INSIGs bind to SCAPs and prevent them from activating sterol synthesis.
What does FXR do?
Increases BSEP activity, increased Bile salt export pump.
Increases SHP activity, which inhibits LXR
How is cholesterol synthesis induced by low cholesterol, in the liver?
SREBP-2, an ER-integral membrane protein
SREBP-2 binds to SCAP in the ER membrane,
SREBP-2-SCAP complex moves to the golgi and is cleaved
SREBP-2 is cleaved into fragments which go to the nucleus and bind DNA SRE, inducing increases HMG-CoA synthesis.
Low cholesterol also increases LDL-receptor expression to obtain fats.
How is Cholesterol taken up by peripheral cells?
By the LDL receptor
How is cholesterol exretyed by peripheral cells?
Under control of the LXR transcription factor.
Antithrombotic mediators of endothelial cells
Anticoagulant effect of endothelial cells
Fibrinolytic effect of endothelial cells
Cytokines establising smooth muscle tone of the Aorta
Anti-inflammatory effect of endothelial cells
Inhibition of adhesion and migration of leukocytes.
Changes in expression by dysfunctional endothelial cells
more leukocyte adhesion
monocyte and macrophage chemotaxis
Possible sources of ROS
has low affinity for LDL receptor and longer half life, thus more oxLDL.
peroxidation of plasma membrane
peroxidation of LDL
How do macrophages damage endothelium and contribute to atheroma
Trapping in the endothelium
Foam cell generation
sdLDL and oxLDL accumulation,
Components of an atheroma
Dysfunctional/damaged endothelium overlying
Macrophages, Foam cells,
Smooth muscle cells
Atherosclerosis risk factors
B6 vitamin deficiency
What causes familial hypercholesterolemia
LDL receptor mutations
ApoA1 mutation, low HDL
LPL deficiency is NOT a risk factor.
Medical treatments for atherosclerosis
Statins inhibit HMG-CoA reductase
VLDL exocytosis inhibitors
PPAR activators, called fibrates.