Lecture 27 - Atherosclerosis Flashcards
What occurs after initial intima injury?
After initial intima injury, remodelling of media (atrophy, loss of SMC’s) occurs to accommodate plaque and preserve lumen diameter
Where does atherosclerosis begin?
In the intima
Where is the most common location for atherosclerosis?
Coronary arteries
What does atherosclerosis in the coronary arteries cause?
Coronary artery disease
What does atherosclerosis in the cerebral (carotid) arteries cause?
Transient ischemic attack (TIA) or stroke
What does atherosclerosis in the limb arteries cause?
Peripheral artery disease
What does atherosclerosis in the renal arteries cause?
Hypertension or kidney failure
What are aneurysms in atherosclerosis?
Bulge in artery which can be life threatening if burst
What is the process of atherosclerosis/endothelial dysfunction?
Initial injury
Fatty streak
Intermediate lesion
Atheroma
Fibroatheroma
Complicated lesion
What can be the initial injury of endothelium?
Hypercholesterolemia
- High cholesterol
Hypertension
High triglycerides (FFA)
Inflammation
What is the bad form of cholesterol?
LDL
What does LDL do?
Stick to artery walls leading to plaque formation
What does HDL do?
Carry LDL away from artery walls
What are the HDL cholesterol levels and risk classification?
< 1.0 mmol/L High Risk
> 1.6 mmol/L Desirable level
What are the LDL cholesterol levels and risk classification?
< 2.6 mmol/L Optimal
> 4.1 mmol/L High Risk
What is the formation of fatty streak?
Influx of LDL exceeds eliminating capacity – extracellular LDL pool
LDL migrate to subendothelial intima
oxLDL- expression leucocyte adhesion molecules - chemokine secretion to attract monocytes
LDL oxidized by radicals - oxLDL
Monocytes enter the intima
Monocytes turn into Macrophages to take up the excessive oxLDL
Macrophages internalise oxLDL
Dead macrophages - Foam cells
Foam cells attract more monocytes and form fatty streak
What is the formation of plaque?
Foam cells activating T-cell immune response
Smooth muscle cells (SMCs) migrate from media into the
intima, and turn into fibroblast like repair cells
Synthesise extracellular matrix: elastin and collagen
Developing calcium crystals
Inflammatory response (C-reactive protein)
Formation of fibrous cap
Isolating the stiffened lipid core prevents blood clothing
Plaque = lipid core and fibrous cap
What does lesions and fissures of endothelium cause?
Formation of thrombus (blood clot) on plaque
What is arterial/venous thrombosis?
Formation of a thrombus within artery or vein
What is arterial/venous embolism?
Interruption of blood flow due to an embolus (free-moving thrombus), potentially causing infarction of almost any organ/part in body
During the formation of a fibrous cap:
a. monocytes turn into macrophages and take up the excessive oxLDL particles.
b. smooth muscle cells migrate into the media.
c. the clinical risk for an arterial thrombus is very high.
d. calcium crystals are formed in the intima.
d. calcium crystals are formed in the intima
What takes up the excessive oxLDL?
Monocytes which turn into macrophages in tissue
- Macrophages internalise oxLDL
What do the foam cells do?
Attract more monocytes to form fatty streak
Activate T-cell immune response
What do smooth muscle cells (SMCs) do during plaque formation?
Smooth muscle cells (SMCs) migrate from media into the intima, and turn into fibroblast like repair cells that synthesise extracellular matrix (elastin and collagen) - fibrosis
