ATHEROSCLEROSIS & LIPID LOWERING DRUGS

Question 1

what is atherosclerosis characterised by ?

Answer 1

a chronic inflammation of the blood vessel wall.

Question 2

what does atherosclerosis lead to ?

Answer 2

vessel narrowing, occlusion(blockage or closing of a blood vessel), and distal ischaemia

Question 3

what is the main cause of death in the western world ?

Answer 3

cardiovascular disease

Question 4

give three hallmarks of cardiovascular disease ?

Answer 4

activation of leukocytes and platelets
vascular smooth muscle hypertrophy
modification and disposition of lipid

Question 5

what are platelets

Answer 5

cell fragments involved in clotting

Question 6

what is hypertrophy ?

Answer 6

enlargement of a tissue due to the increase in size of its constituent cells

Question 7

what is atherosclerosis ?

Answer 7

a disease of the arteries characterised by the deposition of fatty material on their fatty walls

Question 8

what is ischaemia ?

Answer 8

inadequate blood supply to an organ, especially the heart muscles.

Question 9

what are the sequence of events that lead to atherosclerosis ?

Answer 9

1. endothelial dysfunction - loss of cytoprotective mediators
2. macrophages are activated and adhere to endothelium
3. manufacture of reactive oxygen species by macrophages leads to low density lipoprotein (LDL) oxidation and further damage to endothelium
4. modified LDL not cleared from plasma
5. macrophages take up modified LDL and migrate into the vessel wall (foam cells)
6. platelets also activated and adhere to endothelium
7. macrophages and platelets release cytokines, growth factors to cause hyperplasia, further damage and attract additional cells.

Question 10

what is atherosclerosis commonly associated with ?

Answer 10

increased risk of heart attack due narrowing and hardening of arteries

Question 11

what is cytoprotection ?

Answer 11

Cytoprotection is a process by which chemical compounds provide protection to cells against harmful agents

Question 12

what triggers atherosclerosis ?

Answer 12

endothelial dysfunction and loss of cytoprotective mediators:
Nitric Oxide (NO)
Prostacyclin (PGI2)
Endothelium-derived hyper polarising factor (EDHF)

Question 13

what is atherogenesis ?

Answer 13

formation of fatty acids in arteries

Question 14

how do endothelial mediators act in concert to oppose atherogenesis ?

Answer 14

Inhibit activation of leukocytes and platelets
prevent vascular smooth muscle proliferation
vasodilators
promote regeneration of damaged/lost endothelium

Question 15

what is cholesterol ?

Answer 15

is a sterol, type of lipid molecule, and is biosynthesised by animal cells and is key to the membranes structural integrity ad fluidity

Question 16

what is cholesterol linked to ?

Answer 16

CVD

Question 17

what are the important physiological functions of cholesterol ?

Answer 17

integral component in the synthesis of steroid hormones
structural importance in cell wall
fat-soluble vitamin synthesis (e.g. vit D)

Question 18

how are lipids transported in plasma ?

Answer 18

because of their hydrophobicity they are transported as complexes with proteins - macromolecular complexes called lipoproteins

Question 19

how are fatty acids transported ?

Answer 19

fatty acids are associated with albumin

Question 20

what do lipoproteins have at their core ?

Answer 20

lipid (triglyceride and and cholesterol ester)

Question 21

what is the coat of lipoproteins composed of

Answer 21

phospholipid, free cholesterol and protein (apoprotein)

Question 22

how are lipoproteins classified ?

Answer 22

by their size/density.

Question 23

what are four types of lipoprotein ?

Answer 23

High density lipoprotein
low density lipoprotein
very low density lipoprotein (VLDL)
Chylomicrons

Question 24

what is often termed good cholesterol ?

Answer 24

HDL because it transports lipid from periphery to liver (for removal) and steroidogenic organs (e.g ovaries, testes)

Question 25

what is often termed bad cholesterol ?

Answer 25

LDL transports lipid form liver to cells in need of it. These cells express Low density lipoprotein receptors (LDLR).

Question 26

what is the link between hyperlipidemia and atherosclerosis

Answer 26

These studies provide new insight into the complex mechanisms wherby hyperlipidemia causes progressive atherosclerosis

Question 27

what do metabolic disorders do ?

Answer 27

alter lipid transport to give primary (genetically determined ) or secondary (resulting from other disease, e.g. diabetes) hyper