biochemistry 7 Flashcards
what is atherogenesis
process that leads to narrowing or sudden complete occlusion of the arterial lumen
- lipid deposition in the subendothrlial layer
what are the arteriosclerotic cardiovascular diseases
- coronary heart disease
- stroke
- peripheral vascular disease
what are the complications of atherosclerosis
- renal artery disease
- aneurysms
- coronary heart disease
- stroke
- peripheral artery disease
what are the major stages of atherosclerosis
1) endothelial dysfunction
2) formation of lipid layer within the intima
3) monocytes and smooth muscle cells migrate into vessels wall forming macrophages
4) foam cell formation - cholesterol as detergent
5) degradation of extracellular matrix —-> plaque formation and displacement
what is calcification and what does it cause
- calcium build up in plaques
- > 5 years after plaque formation
- problem in over 40s
- arteries stiff, reduced expansion/contraction
- more difficult to treat
what does a normal endothelial cell do
- high kruppel-like factors (KLF2,KLF4) - anti-inflammatory control
- low NFxB - proinflammatory factors
what does dysfunctional endothelium cells do
- KLF factors suppressed
- NFxB predominates - increases expression of cell-adhesive moclules and promotes adhesion of monocytes and T lymphocytes to the endothelium
- decreases NO production - promotes vasoconstriction
what are the inflammatory autoimmune conditions and what do they do
- rheumatologic disorders
- systemic lupus erythematosus
- they elevate systemic inflammation
what are the risk factors for elicit pro-inflammatory cytokines
- Interleukin-1 (IL-1)
- Tumour necrosis factor-alpha (TNF-α)
- Interferon (IFN)
what are the accentuated traditional factors for atherosclerosis
- dyslipidemia
- smoking
- hypertension
- physical inactivity
- insulin resistance
- obesity
how does HDL protect against atherosclerosis
- HDL removes cholesterol from macrophages
- cholesterol returned o liver - generates bile salts or excretion
what occurs when there is a blockage of cholesterol transferred to HDL
- premature atherosclerosis
what is the function of cholesterol
- modulates membrane fluidity
- some nerve cells have 25% plasma membrane
- precursor for steroid hormones
how much cholesterol is found in the brain
- 25% of bodies cholesterol
what changes in pathways can cause Parkinson’s disease
- decreased cholesterol
- increases eicosanoids
- increases DAG, TAG and glycerophosphoinositol
- decreased sphingomyelin
- increased ceramide and gangliosides
what are the treatments to decrease fat
- decreased fat intake
- exercise
- medical intervention
what does increasing LDL receptors via treatment do
- increased DL uptake from the blood —> increase cholesterol clearance
what happens when using treatment to decrease cholesterol precursors
- inhibit bile salt - ingesting a charged resin that binds to bile salts decreasing reabsorption
- inhibits HMG CoA reductase - by statins which decreases cholesterol synthesis
what do PCSK9 inhibitors to
- targets LDL receptors via degradation
- inhibitors are monoclonal antibodies
what do fibrates do
- agonists of PPAR alpha transcription factor
- stimulates lipoprotein lipase - decreases plasma triglyceride concentration and increases HDL
what does niacin do
- binds niacin receptors
- reduce free fatty acid release from adipose
- inhibits HDL uptake by the liver
overall: - raise HDL
- lower LDL
- lower triglycerides
