Fundamentals Of Atherogenesis Flashcards
What is the main problem of atherogenesis?
When the plaque ruptures, a thrombus will form, leading to arterial blockage and eventually death
What are risk factors for atherogenesis?
Modifiable Tobacco smoking High serum cholesterol Hypertension Obesity Uncontrolled diabetes Unmodifiable Age Family history
What is the distribution of atherosclerotic plaques?
Found within peripheral and coronary arteries. Focal distribution
What is the distribution of atherosclerotic plaque distribution governed by?
Change in flow/turbulence - bifurcations cause the artery to alter endothelial cell pattern
Wall thickness change - leading to neointima (scar tissue)
Altered gene expression in the key cell types
What does an atherosclerotic plaque consist of ?
Lipid
Necrotic core
Connective tissue
Fibrous “cap”
What does the fibrous cap consist of?
Smooth muscle cell extracellular matrix
Consequences of the plaque?
It can occlude (angina) or it may rupture (thrombus formation)
What is the response to injury hypothesis of atherosclerosis
Injury to the endothelial cells leading to endothelial dysfunction
Signals sent to circulating leukocytes which then accumulate and migrate into the vessel wall
Inflammation ensures
What initiates inflammation in the arterial wall?
LDLs and endothelial dysfunction
How do LDLs initiate inflammation in the arterial wall?
They can pass in and out of the arterial wall in excess, accumulate in the arterial wall and undergoes oxidation and glycation
What is the stimulus for adhesion?
Once initiated chemoattractants are released from endothelium and send signals to leukocytes. Chemoattractants are released from site of injury and a concentration gradient is produced
Inflammatory cytokines found in plaques
IL-1, IL-6, IL-8, IFN-y, TGF-B, MCP-1 and CRP
Role of IL-6
Pro-inflammatory cytokine and an anti-inflammatory myokine
Role of IL-8
Attracts and activates neutrophils in inflammatory regions
Role of IFN-y
Activator of macrophages and inducer of Class II MHC molecule expression
Role of TGF-B
Transforming growth factor beta 1. Secreted protein that performs many cellular functions - cell growth, proliferation, differentiation and apoptosis
Role of MCP-1
Monocyte chemoattractant protein-1
Steps of leukocyte recruitment to vessel walls
Capture, rolling, slow rolling, firm adhesion and transmigration
Type of molecules used during the steps of leukocyte recruitment to vessel wall
Capture, rolling and slow rolling - selectins
Firm adhesion and transmigration - integrins and chemoattractants
Describe fatty streaks
Earliest lesion of atherosclerosis
<10 years
They consist of aggregations of lipid-laden macrophages and T lymphocytes within the intimal layer of the vessel wall
Describe intermediate lesions
Composed of layers of: Foam cells Vascular smooth muscle cells T lymphocytes Adhesion and aggregation of platelets Isolated pools of ECF
Describe fibrous plaques/advanced plaques
Impedes blood flow Prone to rupture Covered by dense fibrous cap made of ECM proteins - collagen (strength) and elastin (flexibility) May be calcified Contains SMC Macrophages Foam cells T lymphocytes
Describe plaque rupture
Plaques constantly growing and receding
Fibrous cap needs to be resorbed and redeposited in order to be maintained
if balance shifts towards inflammatory/enzymatic conditions the cap becomes weak and the plaque ruptures
Basement membrane, collagen and necrotic tissue exposure as well as haemorrhage of vessels within the plaques
thrombus clot formation and vessel occlusion
Describe plaque erosion
Second most prevalent cause of coronary thrombosis
Lesion tends to be small early lesions
Fibrous cap does not disrupt
Luminal surface underneath the clot may not have endothelial present but is SMC rich
Prominent lipid core
