ERM2- Cholesterol

  1. Hypercholesterolemia: Epidemiology
    • -1/6 teenagers has atheromas
    • ->85% of ppl over 50 have atheromas
  2. Liver Cholesterol pathway
    • -liver makes vLDL
    • -endothelial lipoprotein lipase cleaves off FAs --> IDL
    • -IDL loses more TGs --> LDL
    • -LDL is taken up by hepatocytes via LDLR
    • -LDL is digested to release XOL
    • -XOL is used for cellular functions
  3. Exogenous Cholesterol Pathway
    • -fat is absorbed through the intestines --> forms chylomicrons
    • -chylomicrons are metabolized by LPL in the capillaries to chylomicron remnants
    • -remnants are metabolized in the liver
  4. HDL
    • -high CE content
    • -picks up TGs from vLDL, LDL and IDL in the periphery
    • -takes it to the liver to be secreted in the bile

    * all cells make XOL but only liver can degrade it
  5. Therapeutic Goals
    • LDL < 130 with no risk factors
    • LDL < 100 with risk factors

  6. LDL Receptor Regulation
    • -expressed in liver and peripheral tissues
    • -cells can control LDLR expression
    • -downregulated with cell gets 2.5 mg of XOL
  7. Treatment: Niacin
    -Niacin blocks export of vLDL
  8. Treatment: Bile Acid Binding Resins
    • -resings bind bile acid and prevent it from being recycled
    • -depletes critical pool of liver xol
    • -liver upregulates LDLR and increases uptake of LDL from circulation

    • Adverse Effects:
    • -hard to take
    • -constipation
  9. Treatment: Statins
    • -inhbit HMG CoA Reductase
    • -depletes critical pool of xol in liver --> LDLR upregulation
    • ***only work in people with a functional LDLR


    • Adverse Effects:
    • -myopathy
    • -increase liver enzymes
  10. Treatment: Selective Cholesterol Absorption Inhibitors (CAIs)
    • -ezetimibe
    • -inhibits xol absorption at enterocytes
    • -depletes critical pool of xol --> increased LDLR
    • -often combined with statins

    ***no effect on fat soluble vitamins
  11. Future Therapies: mipomersen
    • -antisense oligonucleotide for ApoB
    • -inhibits formation and release of vLDL
    • -lowers LDL 35% on top of other therapies
Card Set
ERM2- Cholesterol
Endocrine and Reproductive Pathology