Atherosclerosis

Question 1

Define

VLDL

Answer 1

very low density lipoproteins

• unable to pass through the BV wall

contain the Apo B 100 ligrand for LDLD reuptake

Question 2

Define

LDL

Answer 2

low density lipoproteins “cholesterol”

• can easily penetrate the BV
• contains ApoB100

Question 3

Define

Lp(a)

Answer 3

formed from LDL and contains the ApoB100

• is similar to and competes with plasminogen

Question 4

Define

HDL

Answer 4

high-density lipoproteins

• also cholesterol
• many species
• all contain ApoAI which is protective

Question 5

smallest to biggest lipoproteins

Answer 5

HDL, LDL, VLDL, Chylomicron

Question 6

reverse cholesterol transport

Answer 6

HDL removes excess cholesterol from cells, gets incorp into ApoAI

Question 7

Exogenous pathway of lipoprotein transport

Answer 7

triglycerides/cholesterol from GI–> intestinal lymph( transported in chylomicrons–> plasma where they’re hydrolysed to enter muscle for energy and adipose for storage

Question 8

Endogenous pathway for lipoprotein transport

Answer 8

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

Question 10

T/F

Strong pos correlation between plasma LDL and atherosclerosis/CHD

Answer 10

True

Question 11

T/F

negative correlation between plaque Lp(a) and CHD

Answer 11

false as Lp(A) competes with plasminogen thus increased Lp(a) leaders to reduced plasminogen and thus increased thrombus formation

Question 12

T/F

Atherosclerosis is linked to early evidence of endothelial dysfunction

Answer 12

True

Question 13

Pathogenesis of Athersclerosis

Answer 13

• 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

Question 14

CRP

Answer 14

• Informs on statin therapy
• predictive of CVD and inflamm as more CRP means more inflamm
• stimulated by IL-6 from inflamm cells

Question 15

Primary causes of hyperlipidemia

Answer 15

• hypercholesterolemia
• hypertriglyceridemia
  
  • both

could be genetic from conditions like FH where there is a defect in the LDL receptor

could be from dietary excess

Question 16

Secondary causes of hyperlipidemia

Answer 16

because of other diseases e.g diabetes mellitus, alcoholism, obstructive liver disease, drugs

Question 17

Feedback Inhibition in LDL brekadown

Answer 17

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.

Question 18

Treatment of Hyperlipidemia

Answer 18

• 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

Question 19

Drugs used for hypercholesterolemia

Answer 19

STATINs and PCSK9 inhibitors

Question 20

STATINS

Answer 20

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

Question 22

when to admin STATINS

Answer 22

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

Question 24

PCSK9

Answer 24

circulating serine protease that binds to LDL receptors and facilitates its lysosomal degradation

Question 25

Evolocumab

Answer 25

Inhibitor of PCSK9