Atherosclerosis Flashcards
Define
VLDL
very low density lipoproteins
- unable to pass through the BV wall
contain the Apo B 100 ligrand for LDLD reuptake
Define
LDL
low density lipoproteins “cholesterol”
- can easily penetrate the BV
- contains ApoB100
Define
Lp(a)
formed from LDL and contains the ApoB100
- is similar to and competes with plasminogen
Define
HDL
high-density lipoproteins
- also cholesterol
- many species
- all contain ApoAI which is protective
smallest to biggest lipoproteins
HDL, LDL, VLDL, Chylomicron
reverse cholesterol transport
HDL removes excess cholesterol from cells, gets incorp into ApoAI
Exogenous pathway of lipoprotein transport
triglycerides/cholesterol from GI–> intestinal lymph( transported in chylomicrons–> plasma where they’re hydrolysed to enter muscle for energy and adipose for storage
Endogenous pathway for lipoprotein transport
cholesterol/triglycerides synth in the liver are transported as VLDL to muscle/adipose tissue
- in muscle and tissue they’re hydrolysis to form lipoprotien particles which become LDL
T/F
Strong pos correlation between plasma LDL and atherosclerosis/CHD
True
T/F
negative correlation between plaque Lp(a) and CHD
false as Lp(A) competes with plasminogen thus increased Lp(a) leaders to reduced plasminogen and thus increased thrombus formation
T/F
Atherosclerosis is linked to early evidence of endothelial dysfunction
True
Pathogenesis of Athersclerosis
- Vascular cholesterol take up by LDL receptors on Endothelium
- oxidation of LDL causes increased adhesion
- Monocytes recruited into the arterial wall
- upon entry diff into macrophages
- macrophages create inflamm environment as they become foam cells
- T cell enter and release cytokines which cause more inflamm
CRP
- Informs on statin therapy
- predictive of CVD and inflamm as more CRP means more inflamm
- stimulated by IL-6 from inflamm cells
Primary causes of hyperlipidemia
- hypercholesterolemia
- hypertriglyceridemia
- both
could be genetic from conditions like FH where there is a defect in the LDL receptor
could be from dietary excess
Secondary causes of hyperlipidemia
because of other diseases e.g diabetes mellitus, alcoholism, obstructive liver disease, drugs
Feedback Inhibition in LDL brekadown
increased LDL intake/ increased intracellular cholesterol leads to decrease in HMG CoA reductase( coenzyme involved in intracellular production of cholesterol) and decreased in LDL receptor gene transcription.
Treatment of Hyperlipidemia
- consider their CV status and risk factors
- if it is secondary to other diseases we treat these first
- dietary and lifestyle modif before any drug intervention
Drugs used for hypercholesterolemia
STATINs and PCSK9 inhibitors
STATINS
competetively Inhibits the HMG-CoA reductase enzyme which converts HMG-CoA to cholesterol endogenously thus inhibits endogenous cholesterol production in hepatocytes which promoted LDL receptor expression and thus LDL clearance.
- after patients have very low LDL, low TG, and high HDL as well as see an improvement in endothelial function and plaque stabilisation
- e.g simvastatin, pravastatin, atovastatin
when to admin STATINS
for primary prevention for CVD( people with high risk and have elevated cholesterol)
for people with high risk of CHD regardless of chol levels
as secondary prevention of MI and stroke as these indivs are likely to have underlying vasc disease
PCSK9
circulating serine protease that binds to LDL receptors and facilitates its lysosomal degradation
Evolocumab
Inhibitor of PCSK9
