Atherogenesis and Atherosclerosis Flashcards
Risk factors for atherosclerosis
Incr age (>45 for M, >55 for F), diabetes, family Hx of premature CHD (1st degree M relative
When does atherosclerosis begin?
Fatty streaks in childhood (50% of 2-15 yo autopsies, 85% 21-39 yo), coronary atheromas (8% 2-15 yo, 33% 16-20 yo, 52% 21-25 yo, 69% 26-39 yo)
What is atherosclerosis?
Response to chronic stress or injury to blood vessels
Describe the layers of a normal muscular artery
Tunica intima (endothelia, internal elastic lamina), tunica media (smooth musc responding to endocrine and paracrine signals), tunica adventitia (external elastic lamina, neurogenic plexus, CT)
Functs of normal endothel w/ normal NO levels.
controls shear stress, prevents WBC adhesion, promotes vasodilation, inhibits platelets adhesion, normal t-PA:PAI-1 promotes fibrinolysis.
Describe the process of atherogenesis.
Excess LDL to subendothelial space, gets oxidized, and trapped in the sub-endothelial space. Secretes signals that attract monocytes/macrophages. M/MPs activated and in sub-endothel space to become foam cells that scavenge the oxidized LDL and thicken the arterial wall.
How do platelets contribute to atherosclerosis?
Dyfunctional/damaged endothel allows platelet aggregation. Aggregated platelets release SMC growth factors, promoting proliferation, allowing SMC migration in sub-endothel space.
What is Vascular Cell Adhesion Molec?
A cytokine-regulated mononuclear leukocyte adhesion molec, binds monocytes and lymphocytes. Expressed by endothel over fatty streaks and microvessels of mature atheromas.
What is monocyte chemoattractant prot-1?
A potent mononucl chemoattractant produced by endothel and smooth musc. Its absence reduces atherosclerosis.
What is Macrophage Colony-Stimulating Factor?
A potent monocyte activator and co-mitogen produced by endothel and smooth musc cells. Localizes in human and experimental atheroma and augmented M-CSF gene expression in human and experimental atherogenesis.
What is the role of VCAM-1, MCP-1, and M-CSF in atherogenesis?
V-CAM1= WBC adhesion MCP1= WBC migration to sub-endothelial space M-CSF= aggregation of foam cells eating up the LDL
How much stenosis is needed to cause an MI?
Steps of arterial remodeling in atherosclerosis
- compensatory expansion (wall gets bigger/wider)
2. expansion ability is overcome and plaque accumulates into the lumen (lumen narrows)
What is the limitation of looking just inside the arteries to predict MI?
Tools don’t measure athero burden very well, what is going on inside the wall (is it expanding outward?), can’t tell what the material in the wall in made of (thick fibrous cap vs. thin cap w/ lipid core).
Main cause of lumen blockage in atherosclerosis that leads to an MI?
thrombus when plaque has a tear at the shoulder region (where the membrane is thinner), leading to hemorrage that fills the space, clots, and pushes the fibrous cap that remains into the lumen.
