1b Atherosclerosis Flashcards
How is the world disease burden of coronary heart disease changing?
Increasing levels of obesity and diabetes globally
What are the modifiable risk factors of coronary heart disease?
Smoking, Lipids intake, blood pressure, diabetes, obesity and sedentary lifestyle
What are the non-modifiable risk factors for atherosclerosis?
Age
Sex
genetic background
What are the three risk factors which contribute to the risk factor multiplication?
Hypertension
High Cholesterol
Smoking
Why has hyperlipidaemia reduced over the last decade?
Statin treatment
How has hypertension changed over the last few decades?
Lowered due to anti-hypertensive treatment
What are the function of vascular endothelial cells?
barrier function eg to lipoproteins
involved in leukocyte recruitment
What is the role of platelets in atherosclerosis?
Thrombus generation
Cytokine and growth factor release
What are monocyte-macrophages involved in?
Foam cell formation, and the release of cytokines and growth factors
What are a major source of free radicals?
Monocytes/macrophages
What are the roles of vascular smooth muscle cells?
Migration and proliferation
Collagen Synthesis
Remodelling and fibrous cap formation
Which T lymphocytes are involves in macrophage activation?
CD4 Th1
Which T lymphocytes are involved in macrophage de-activation?
CD4 Treg
What is the main basis of atherosclerosis?
Inflammation
What is the connection between lipids and inflammation in atherosclerosis?
Cholesterol crystal formation connects lipids and inflammation in atherosclerosis
What happens if white blood cells are activated excessively?
White blood cells can damage host tissue if they are activated
What are the main inflammatory cells in atherosclerosis?
Macrophages - derived from blood monocytes
What regulates macrophages?
Combination of transcription factors binding to regulatory sequences on DNA
What are the two types of macrophages?
Inflammatory macrophages and non-inflammatory / resident
macrophages
What are inflammatory macrophages adapted to do?
Kill micro-organisms 9germs)
What are the functions of non-inflammatory macrophages?
Normally homeostatic functions
Alveolar resident macrophages = involved in surfactant lipid homeostasis
Spleen = involved in iron homeostasis
What is LDL?
Low density lipoprotein - the “bad” cholesterol which is made in the liver
What is the function of LDL?
Carries cholesterol from the liver to the rest of the body including the arteries
What is HDL?
High density lipoprotein - carries. cholesterol from the peripheral tissues including arteries back to the liver = involved in reverse cholesterol transport
What causes modified LDLs to form?
Free radicals, enzymes and aggregations
What do modified LDLs form?
Families of high inflammatory and toxic forms of LDL found in vessel walls
What is the surrounding layer of lipoproteins like?
Lipid monolayer which is one molecule thick - separates fat from water
Contains apoproteins on the surface
What is carried in the center of an LDL?
triglycerides
Why do LDLs leak through the endothelial barrier?
Due to activation in areas of vortex
What traps the LDL in the sub-endothelial layer?
It binds to sticky matrix carbohydrates (proteoglycans) and sticks in the sub-endothelial layer - becomes susceptible to modification
What type of modification might a LDL undergo?
oxidation - through free radical attack from activated macrophages
What happens to the LDL once it has been oxidatively modified?
Phagocytosed by macrophages which stimulates chronic inflammation
What do the engulfed oxidised LDL’s become?
Foam cells = leads to chronic inflammation
What is seen in children with familial hyperlipidaemia?
Xanthoma - lesions containing cholesterol and fat