L41 – Atherosclerosis and disrupted circulation Flashcards
(43 cards)
Define atherosclerosis
A process of progressive thickening and hardening of the walls of medium-sized and large arteries as a result of fat deposits on their inner lining.
What is the precursor lesion to atheroma?
Lipid/ fatty streak
What are fatty streaks?
Lipid deposits in intima, flat / slightly elevated streaks
What are some irreversible risk factors of atherosclerosis?
Age, Sex, Genetics
- Increase risk with age
- Male more likely to die from IHD than female up to 75 years old
- Genetic hyperlipidemia, hypertension
What are some reversible risk factors of atherosclerosis?
- Smoking
- Hyperlipidemia
- Hypertension
- Diabetes
- Hyperomocysteinaemia (caused by renal/ liver disease or diet deficiencies)
How does smoking increase risk of atheroma?
Damages endothelium > causes leukocytes to stick (adhere) to vessel wall
Decreases ability of vessels to relax / dilate
How does hyperlipidemia increase risk of atheroma?
oxy-LDL is critical to start atheroma formation in tunica intima
Low HDL levels mean accumulation of lipid
How does hypertension increase risk of atheroma?
Mechanical injury to endothelium by applying shear stress
How does Diabetes increase risk of atheroma?
- raised LDL levels,lower HDL levels due to abnormal lipoprotein metabolism
- Renal failure > accumulate homocysteine
- Advanced Glycation Endproduct (ACE)
How does hyperhomocysteinaemia increase risk of atheroma?
homocysteine auto-oxidises > reacts with reactive oxygen species to damage endothelial cells > stimulate formation of thrombi (stimulate FA-synthesis and fibrous cap formation too)
What starts formation of atheroma?
Fluid shear stress damages endothelium > LDL in blood can enter
What happens to LDL entering intima at the start of atheroma formation?
oxidized by reactive oxygen
species within vessel wall > form oxidized low density lipoprotein (oxLDL)
What do oxidized low density lipoprotein (oxLDL) stimulate production of ?
stimulate production of
cytokines / growth factors (ICAM-1, VCAM-1, P-, E- selectins) within intima > monocytes adhere to
arterial endothelium
What happens after monocyte adherence in formation of atheroma?
Adhered monocytes penetrate into artery > grow into macrophages> along with smooth muscles cells phagocytose oxLDL through scavenger receptors (e.g. CD36, SR-A)
What happens after macrophage uptake oxLDL ?
phenotypic modulation > apoptosis / necrosis > release extracellular debirs/ lipids to form atheroma and produce cholesterol-rich foam cells
What do cholesterol-rich foam cells initiate?
fatty streak
What stimulates SMC to form fibrous cap?
Homocysteine stimulates SMC to proliferate > produce matrix > forms fibrous cap
High levels of homocysteine can upregulate what?
Fatty acid synthesis
Smooth muscle migration
How does increased glucose in diabetes patients exacerbate atherosclerosis?
Increased glucose adhere to amino acids in collagen > form Amadori Products (AGE) > recognized by macrophages, platelets > release cytokines + cause damage to ECM > accelerate tissue stiffening and accelerate sclerosis
How can infection worsen atheroma?
Infection > systemic inflammation > cytokines stimulate coagulation and vasoconstriction
What growth factor is responsible for change in SM arrangement in atheroma?
platelet-derived growth factor (PDGF)
Stimulate smooth muscle proliferation
Attract migration of SMC from media to intima
What growth factor is produced by damaged endothelial cell and worsens atheroma?
endothelial cell growth factor (ECGF)
interleukin-1
What happens to the endothelium of fibrous cap in its coagulation properties?
Normal = anti-coagulation
Fibrous cap = Pro-coagulation
What is the difference between atherosclerosis and thromosis?
Atherosclerosis = deposition of fatty material on the inner walls of their arteries
thrombosis = local coagulation or blood clot in a part of the circulatory system.
