Lecture 11 - Atherosclerosis Flashcards
What is Arteriosclerosis?
The thickening of the walls of arteries and arterioles often associated with loss of elasticity
(usually as a result of hypertension or diabetes Mellitus )
What can happen as a result of Arteriosclerosis?
Poor tissue perfusion
Inelastic/weak vessels which can lead to aneurysm
Increased risk of thrombus formation
What is Atherosclerosis?
Accumulation of intracellular and extracellular lipid in the tunica intima and media of medium - large sized arteries
What is an Atheroma?
A necrotic core of the atherosclerotic plaque
The thickening and hardening of arterial walls as as consequence of atherosclerosis
What is contained in the tunica adventitia of blood vessels?
Blood vessels and nerves that supply the vessels
Thick collagen and elastin layer
What are the 2 main events that lead to the development of atherosclerotic plaques?
Endothelial damage
Inflammation
What can lead to endothelial damage?
Hyperlipidaemia (High LDL)
Hypertension
Smoking (toxins)
Haemodynamic stressors
What does Endothelial dysfunction lead to?
Platelet adhesion
Smooth muscle cell proliferation and migration
Lipids (LDL and cholesterol) cross into the tunica Intima
Monocytes (macrophages) cross into intima
What cells end up forming foam cells?
Macrophages
Smooth muscle cells
What is the function of the macrophages when the endothelial wall is damaged?
Secrete cytokines recruiting other inflammatory cells
Stimulate more smooth muscle cells
What is the function of the proliferating/migrating smooth muscle cells when endothelial cells are damaged?
Produce matrix material forming the “roof”
Matrix made of collagen, elastin and other proteins
How do smooth muscle cells migrate when the endothelial cells are damaged?
The endothelial cells (Tunica intima layer) is broken so the smooth muscle cells that reside in the Tunica media can slip into the lumen of the vessel
How do macrophages become foam cells?
How do smooth muscle cells become foam cells?
Macrophages engulf oxidised lipids (like LDL)
SM takes up lipids due to receptors they have
What do the smooth muscle cells in the intima and media begin to produce as they form the fatty streak and as the plaque develops?
Fibrous cap reinforced with collagen and elastin
What does the formation of the fibrous cap by the migrated smooth muscle lead to?
Separates the cells in the centre of the plaque from the blood supply
Leads to a necrotic core developing
What are the cellular components of a necrotic plaque?
Macrophages, leukocytes/white blood cells, smooth muscle cells and platelets
What is the function of endothelial cells in atherosclerotic plaque formation?
Produce collagen
Stimulate the proliferation and migration of smooth muscle cells
What is the function of platelets in atherosclerotic plaque formation?
Stimulates proliferation and migration of smooth muscle cells
What is the function of smooth muscle cells in atherosclerotic plaque formation?
Take up LDL and other lipids becoming foam cells
Make collagen and proteoglycans forming the fibrous cap
What is the function of macrophage in atherosclerotic plaque formation?
Oxidise LDL
Take up this oxidised LDL and become foam cells
Secrete proteases which modify matrix
Stimulates proliferation and migration of smooth muscle cells
What is the function of Lymphocytes in atherosclerotic plaque formation?
Produce TNF which can affect lipoprotein metabolism
Stimulate proliferation and migration of smooth muscle cells
What is the function of neutrophils in atherosclerotic plaque formation?
Secrete proteases leading to continued local damage and inflammation
What is an Intima xanthoma?
Fatty streak
What happens in the development of an atherosclerotic plaque?
Fatty streak (Intima xanthoma)
Fibrous cap atheroma (stable plaque)
Thin fibrous cap atheroma
Now prone to rupture and thrombosis
What happens when the fatty streak forms microscopically?
Proliferation of smooth muscles
Foam cells accumulate
Extracellular lipid
What happens microscopically in the stable simple plaque?
Fibrosis (Fibrous cap)
Necrosis
Inflammatory cells