Atherosclerosis Flashcards
What collects in an atherosclerotic plaque?
Inflammatory/immune cells, smooth muscle cells, lipids, connective tissue
What are the three stages of atherosclerotic plaque formation?
- Initiation and formation
- Adaptation
- Clinical
What is a genetic predisposition that can accelerate atherosclerotic plaque formation in the first decade of life?
Homozygous Familial Hypercholesterolemia
Where do atherosclerotic lesions generally form?
Where shear stress is low but fluctuates rapidly
What gene expression increases at sites prone to plaque development? What cells do these genes help recruit?
- Vascular Cell Adhesion Molecule (VCAM-1)
- Intercellular Adhesion Molecule (ICAM-1)
- Proinflammatory Genes
Monocytes/Macrophages
What factors does lipid accumulation depend on?
Disruption of the integrity of the endothelial barrier through cell loss and/or cell dysfunction
Describe the relationship betwixt LDL and atherosclerosis.
- LDL carries lipids into the intima
- Macrophages containing lipids enter intima and undergo necrosis.
- Lipids collect and contribute to plaque formation
What is the likely effect of oxidized lipoproteins in the evolution of atherogenesis?
Ox. lipos. induce tissue damage and recruit macros which can transform the normal anticoagulant vascular surface to a procoagulant one
When a thrombus forms on the early atherosclerotic plaque, what 3 things can occur?
Thrombus may
- Grow
- Lyse
- or become organized and incorporated into the plaque
What occurs when the plaque separates the intima from the nutrient-rich blood?
Intima undergoes ischemic necrosis. Macros as well as platelets release angiogenic factors causing new vaso vasorum to form
What cytokine is a key regulator of ECM deposition in atherosclerotic plaques?
TGF-Beta
Describe the adaptation stage of atherosclerosis
- Plaque protrudes into lumen and the wall of the artery remodels to maintain lumen size
- Once the plaque occupies half of the lumen, remodeling can no longer compensate and the arterial lumen becomes stenotic.
- “Clinically silent”
How can hemorrhage occur in the atherosclerotic plaque?
Fragile new vessels are formed within the plaque and can rupture
What are the two precursor lesions of atherosclerosis?
- Fatty Streaks - Intra/Extracellular lipid accumulation
- Intimal Cell Mass (“cushions” - White, thickened areas at branch points in the arterial tree, NO LIPID
What is the characteristic plaque of atherosclerosis? Characteristics?
The fibroinflammatory lipid plaque; Well defined borders, irregular shape