On: Part III of V: HDL, reverse cholesterol transport, CETP inhibitors, and apolipoproteins.

Episode: 22

Date: October 2018

Key Subjects:

• Old school view of cholesterol transport overly simplified:
  • Forward cholesterol transport (FCT).
    • Delivery of cholesterol by VLDL, LDL and chylomicrons to the cells.
  • Reverse cholesterol transport (RCT).
    • Return of cholesterol to the liver by HDL.
• Leads to erroneous view that HDL is “good” and higher HDL is “better”.
• Forward cholesterol transport observations:
  • VLDL and chylomicrons deliver energy (triglycerides and phospholipids) to the cell, not cholesterol (cells make their own).
    • Cholesterol is part of the lipoprotein to support its spherical structure.
  • After the energy delivery, VLDLs are cleared very quickly.
    • Very few stay around and turn into LDL.
    • Much LDL is made in and comes from the liver directly.
  • LDL is the problem particle as it stays in circulation the longest (days).
    • VLDL half life = half an hour.
• Reverse cholesterol transport observations:
  • HDL not just “good”.
    • As in, it doesn’t only pick up cholesterol and delivers it back to the liver.
    • HDL also transfers cholesterol to other lipoproteins.
      • These particles may take it back to the liver (good).
      • Or stay in circulation (not good).
    • For instance, an LDL particle may get up to 60% of its cholesterol load by bumping into HDL particles.
  • All classes of lipoproteins are involved in the reverse transport, not just HDL.
    • Cholesterol can be taken to many places.
    • Back to the liver, to the intestine or it stays in circulation.
    • If you have a high or low level of HDL-C, it tells you very little about the effectiveness of all the different ways in which HDL is active.
  • Increasing HDL or inhibiting HDL to LDL cholesterol transfer not beneficial.
    • False assumption that higher HDL is good because it results in higher cholesterol clearance.
    • CETP inhibitors (stop HDL to LDL cholesterol transfer) have not proven to be beneficial.

Key Takeaways:

• Disregard HDL number.

Worth Listening:

• 8/10