lipid metabolism 3 Flashcards
What is atherogenesis?
It is a process that leads to the narrowing or sudden complete blockage of the arterial lumen.
What are the complications of atherosclerosis?
- Narrowing of the vessels by fibrous plague
- Weakening of the vessel wall
What are the major stages of the atherosclerosis progression?
- Endothelial dysfunction
- Formation of lipid bilayer within the intima
- Monocytes and smooth muscle cells migrate into the vessel wall and form macrophages
- Cell formation
- Degradation of the extracellular matrix as plague is formed and displaced.
In the normal endothelial what are the anti- inflammatory control factor?
- Low NFKB
In the dysfunctional endothelium what happens to the KLF factors?
they are suppressed
In the dysfunctional endothelium what does the NFKB factors increase?
Increase the expression of the cell adhesion molecules
In the dysfunctional endothelium what does the NKKB factors promote?
adhesion of monocytes and T lymphocytes to endothelium.
in the dysfunctional endothelium what does the NKKB factors decrease?
no production as this promotes vasodilation
what risk factors elicit pro-inflammatory cytokines?
- interleukin 1
- tumour necrosis factor alpha
what does rheumatologic disorders do?
elevate the systemic inflammation.
what does diabetes and LPL deficiency increase?
chylomicrons and VLDL
What is the mutation of the familial dysbetalipoproteinemia?
- apoE
what does familial dysbetalipoproteinemia cause?
Impairment of intermediate density lipoprotein uptake
In the familial hypercholesterolemia where is the mutation caused?
In the LDL receptor
What does familial hypercholesterolemia do?
increase blood LDL
What does familial combined dyslipidemia increases?
- apoB100
- VLDL production
What is familial hypercholesterolemia?
Absence of excessive cholesterol collect in many tissues as LDL becomes oxidised
What is oxidised LDL ingested by?
macrophages
What do macrophages in FH form?
Foam cells- become trapped in blood vessels
What do foam cells lead to?
atherosclerosis
What is Hepatic lipase deficiency?
Affects the body’s ability to break down fat lipids.
What does Hepatic lipase deficiency lead to?
- Decreased secretion of hepatic lipase
- Change in lipoprotein quantity
What is the mutation for the Hepatic lipase deficiency
LIPC gene – recessive hepatic lipase mutations.
what is lysosomal acid lipase deficiency?
it is when they is a build of harmful amounts of fats that is accumulated in the cells and tissues.
what is the mutation of lysosome acid lipase deficiency?
LIPA- gene mutation
what happens in severe lysosomal acid lipase deficiency?
it is rare
the liver and spleen is enlarged
they is fatty stools and jaundice.
what does gut bacteria convert?
excessive dietary choline into trimethyamine.
what does liver convert?
trimethylamine to trimethylamine N- oxide
what does high trimethylamine N-oxide do?
decreases bile synthesis
occurs in antherosclerosis
what does HDL help protect against?
atheroschlerosis
what does HDL do to protect body against atherosclerosis?
- removes the cholesterol from the macrophages
- after it is removed the cholesterol is then returned to the liver and it generates bile salts or exercetion occurs.
what does the blockage of cholesterol transferred to HDL lead to?
premature atherosclerosis
where is lipoprotein lipase mutation found in?
capillaries of muscles and adipose
what are the symptoms of familial lipoprotein lipase deficiency?
- abdominal pain due to inflammation of pancrease
- enlarged spleen and liver
- develops half of fat deposit under the skin
- half fat is content in the blood
- depression, memory loss and mild dementia
what are the treatments associated with familial lipoprotein lipase deficiency?
can be managed by low fat diet
what does Niacin do?
- binds niacin receptors
- reduces fatty acids that is released from adipose
- inhibits HDL uptake by liver
what does ultimately do?
- raises HDL - good cholesterol
- Lowe LDL- bad cholesterol
- lowers triglycerides
what does LDL receptors do?
increases LDL uptake from the blood as it increases cholesterol clearance.
what does the LDL receptors increase via?
decreasing cholesterol precursors
what don increases LDL receptors do?
- inhibits bile salt reabsorption
- inhibits HMG CoA reductase
what do PCSK9 target?
