CVS - Lipid homeostatis Flashcards
What is hyperlipidaemia?
high cholesterol, means you have too many lipids (fats) in your blood
hypercholesterolemia
high cholesterol content.
hyperapobetalipoproteinemia
high levels of apolipoprotein B, which is part of LDL cholesterol.
What is bad cholestrol called?
LDL
What is the genetic type of hyperlipidaemia?
hyperlipidaemia
hypercholestrerolemia
hyperapobetaliprotieinemia
What is the secondary type of hyperlipidaemia caused by
?
- obesity
smoking
high fat diet
alochol
LIPID-LOW
means
- Cholesterol synthesis inhibition
- Intestinal absorption
- Lipoprotein lipase activity
- HDL
Cholesterol synthesis inhibition:
- statins competitively inhibit the HMG-CoA reductase > reduced cholesterol
-Then liver recruits MORE LDL from circulation > LDL clearance from the blood
What are CYP inhibitors?
- grapefruit juice
- diltiazem
- amlodipine
- macrolide antibiotics
worsen statin adverse effects
What are the 1st line therapy for CVD?
- atorvastatin
- pravastatin
- rosuvastatin
-simvastatin
How does cholesterol absorption inhibition work? give an example
- anion exchange resins:
binds with bile salts (insoluble complex) > excreted in faeces
EZETIMDE - block the transport protein Niemann-Pick C1 (in gut wall)
What is the outcome of cholesterol absorption inhibition?
reduced intestinal
cholestrol absorption
cholestrol directed to
compensate for bile loss
LDL cholestrol clearance
Ezetimibe - reduces intestinal cholestrol absorption, without affecting bile
coronary thrombosis
myocardial infarction (MI)
Cholesterol
an essential component that makes the cell membrane and modulates membrane fluidity, and critical for cell growth and viability; Precursor for steroid hormones, vitamin D and bile salts
Triglycerides
largely through diet, but synthesised in the liver as well. supply energy/fuel to muscle and other tissues
How is cholesterol absorbed and transported to the liver?
absorbed by micelles into intestinalw all throigh identified protein channels
bile EMULSIFIES dietery lipids (incl cholestrol), facilitates absorption, salts are recycled via hepatic portal vein (entero-hepatic circulation)
SOME chol. pumped out fo body > away into intestinal lumen by heterodimeric ATP- binding cassette transporter protein complex
Conversion of HMG-CoA to mevaolnate can be stopped, how?
by blocking enzyme, stop secretion of cholestrol
are chol and triglycerides soluble of insoluble in water?
INSOLUBLE - require carrier protein
Characteristics of lipoproteins
central core containing cholesterol esters (hydrophobic)
triglycerides surrounded by free cholesterol, phospholipids (amphophilic)
apolipoproteins, facilitate lipoprotein formation and function
AMPOPHILIC – MIXTURE OF HYDROPHOBIC AND HYDROPHILIC
In core phobic, out phobic – this is how it can move in the blood
Chylomicrons
triglyceride-rich particles made byintestine, transports triglycerides/choletsrol to PERIPHERL tissues and liver
Chylomicron remnants
removal of trigloyceride from chylomicrons by peripheral tissues results in smaller
Intermediate-density lipoproteins (IDL; VLDL remnants)
removal of triglycerides from VLDL by MUSCLE and adipsose tissue results in formation of iDL particles – enriched in cholesterol
sLDL particles
decreased affinity for the LDL receptor resulting in a prolonged retention time in the circulation
How does sLDL get trapped in arterial wall?
easily enters the arterial wall and binds more avidly to intsa-arterial proteoglycans
are sLDL suitable for oxidation?
yes > results in an enhanced uptake by macrophages
HDL, good or bad?
good
- antiapoptotic
- dec, expression of adesion molecules (anti-inflammatory)
- dec LDL oxidation
- ameliorates endothelial function
what do HDL particles contain?
cholestrol and phospholipids
apo A-I is the core structural protein and each - HDL particle may contain multiple Apo A-I moleucles
high levels of Apo-I + atherosclerosis
Pathophysiology of atherosclerosis
1) endothelial dysfunction
2) formation of lipid layer or fatty streak within the intima
3) migration of leukocytes and smooth muscle cells into the vessel wall
4) foam cell formation
5) degradation of extracellular matrix
Increased LDL
plaque rupture
