Atherosclerosis Flashcards
Key components of the
atheromatous plaque (3)
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1 - endothelium
2 - intima (fibrous cap, cellular, necrotic)
3 - media
Development of atheromatous plaques facts (3)
- <20 y ~ 20% already have significant coronary atherosclerosis
- 20-29 y ~ 50%
- 30-39 y it’s up to 65%
Development of atheromatous plaques - types ( + AHA classification) (6)
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1) coronary artery at lesion-prone location: adaptive thickening (smooth muscle), intima + media ~ isolated macrophage foam cells
2) Type II lesion: macrophage foam cells (fatty streak) ~ mainly intercellular lipid accumulation
3) Type III (preatheroma): type II changes and small pools of extracellular lipid
4) Type IV (atheroma): core of extracellular lipid
5) Type V (fibroatheroma): fibrous thickening
6) Type VI (complicated lesion): thrombus, fissure + hematoma
Atheroma (type IV lesion) in proximal left anterior descending coronary artery (3)
Extracellular lipid forms a confluent core in the musculoelastic layer of eccentric adaptive thickening that is always present in this location.
The region between the core and the endothelial surface contains macrophages and macrophage foam cells (fc), but an increase in smooth muscle cells or collagenous fibres is not marked.
A indicates adventitia; M, media. From a 23-year-old man. Homicide was the cause of death.
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Type VI lesion in left anterior descending coronary artery about 2 cm distal to main bifurcation (2)
he type VI lesion is formed by a recent thrombus on the surface of a fibroatheroma. The region between the lipid core and thrombus (Tmb) consists of closely layered smooth muscle cells.
The lipid core also contains cholesterol crystals and dark staining aggregates of microcrystalline calcium (arrows). A indicates adventitia; M, media.
From a 23-year-old man who committed suicide.
Most common sites of plaque build up? (7)
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Internal carotid
Proximal artery
Descending thoracic aorta
Abdominal aorta
Iliac
Femoral
Popliteal
Clinical presentation (5)
- Myocardial infarction
- Stroke
- Aneurysm
- Peripheral vascular disease
- Kidney injury
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Risk factors for atherosclerosis (11)
Age
Male sex (premenopausal women protected)
Genetics
Hyperlipidaemia
Smoking
Hypertension
Diabetes mellitus
Obesity
Metabolic syndrome
Alcohol
Drugs
Age-dependent changes to cardiovascular tissues
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Genetics and CVD (4)
- Cholesterol homeostasis
– apolipoprotein B
– LDL receptor
– PCSK9 (proprotein convertase subtilisin/kexin type 9) - Variants in angiotensinogen associated with hypertension
- Predisposition to type 2 diabetes
- Ion channel proteins affecting arrhythmias
Classic risk factors in the formation and progression of atherosclerotic plaque: possible pathogenic mechanisms of coronary artery disease risk genes
Blue: risk factors associated with metabolic syndrome (MS) and type 2 diabetes (T2D) - microalbuminuria, artherogenic dyslipidemia, hyperglycaemia, obesity, hypertension, inflammation, thrombis
Green: risk factor not directly associated with MS and/or T2D (age, gender, psychology, sedentarism, smoking, lifestyle)
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Classic mechanism of atherosclerosis (6)
1) Injury to the endothelium (dysfunctional endothelium)
2)Chronic inflammatory response
3)Migration of SMC from media to intima
4)Proliferation of SMC in intima
5)Excess production of extracellular matrix
6)Enhanced lipid accumulation
EC function in health and disease
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Initiation of atherosclerosis – A complex inflammatory response? (4)
Endothelial activation: LDL penetrates endothelium + retained in the intima , where it undergoes oxidative modification
- LDL-> intima -> oxLDL -> pro inflammatory lipids sec. from LDL=stim endo cells to express adhesion molecules
Circulating monocytes adhere to endothelial cells expressing VCAM-1 and other adhesion molecules
- monocyte in lumen -> respond to chemokines (e.g. MCP-1) and migrate into intima
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Dynamics of plaque stability (vs Instab) (3)
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Plaque stability:
-concentric architecture
-fibrous rich
-smooth muscle rich
Plaque instability:
-eccentric architecture
-lipid rich
-macrophage rich
-inflammation
-endothelial cell damage
