#240 ‒ The confusion around HDL and its link to cardiovascular disease | Dan Rader, M.D.

79 snips

Jan 30, 2023

Dan Rader, a Professor at the Perelman School of Medicine, dives into the complexities of high-density lipoproteins (HDLs) and their surprising relationship with cardiovascular disease. He emphasizes that high HDL cholesterol does not always mean low disease risk and discusses the importance of HDL functionality over mere quantity. Rader also explores the role of HDLs in reverse cholesterol transport, their link to neurodegenerative diseases, and the latest research that could change how we approach cardiovascular health. It's a deep dive into lipid metabolism that challenges common misconceptions.

Ask episode

AI Snips

Chapters

Transcript

Episode notes

INSIGHT

Lipoprotein Function

Lipoproteins are like oil, they don't mix well with water and need transport vehicles.
These vehicles, called lipoproteins, have a lipid core and surface proteins, enabling transport.

INSIGHT

ApoA1 vs. ApoB

ApoA1, the core protein of HDL, differs from ApoB.
Multiple ApoA1 molecules reside on HDL, and they can exchange between particles, unlike ApoB.

INSIGHT

HDL Biogenesis

ApoA1, secreted by intestines/liver, engages with ABCA1 to acquire lipids.
This lipid acquisition is crucial for nascent HDL formation, shown by Tangier disease.

Get the Snipd Podcast app to discover more snips from this episode

Get the app

View the Show Notes Page for This Episode

Become a Member to Receive Exclusive Content

Dan Rader is a Professor at the Perelman School of Medicine at the University of Pennsylvania, where he conducts translational research on lipoprotein metabolism and atherosclerosis with a particular focus on the function of high-density lipoproteins (HDLs). In this episode, Dan goes in-depth on HDL biology, including the genesis of HDL, its metabolism, function, and how this relates to atherosclerotic cardiovascular disease (ASCVD). He explains why having high HDL-C levels does not directly translate to a low risk of cardiovascular disease and reveals research pointing to a better way to measure the functionality of HDL and predict disease risk. He also goes into detail on the role of HDL in reverse cholesterol transport and the benefits this has for reducing ASCVD. Additionally, Dan discusses the latest thinking around the association between HDL cholesterol and neurodegenerative diseases and ends the conversation with a discussion of how the latest research on HDL provides a promising outlook for ongoing trials and future therapeutic interventions.

We discuss:

The lipidology of apoB and apoA [4:00];
A primer on the high-density lipoprotein (HDL): genesis, structure, and more [9:30];
How the lipoprotein system differs in humans compared to other mammals [20:00];
Clarifying the terminology around HDL and apoA [25:30];
HDL metabolism [31:45];
CETP inhibitors for raising HDL-C: does it reduce CVD risk? [34:45];
Why it’s so important to have hard outcome trials in the field of cardiovascular medicine [42:30];
SR-B1: an HDL receptor important for cholesterol efflux [48:00];
The association between HDL levels and atherosclerosis: are they causally linked? [53:15];
How insulin resistance is impacting HDL, and how HDL-C provides insights into triglyceride metabolism [58:00];
Disappointing results from the studies of niacin—a drug that raises HDL-C and lowers apoB [1:08:15];
HDL lipidation, dilapidation, and reverse cholesterol transport [1:12:00];
Measuring the cholesterol efflux capacity of HDL: a better predictor of ASCVD risk than HDL-C? [1:22:00];
A promising new intervention that may promote cholesterol efflux and reverse cholesterol transport [1:32:45];
The association between HDL cholesterol and neurodegenerative diseases [1:34:00];
Challenges ahead, a promising outlook, and the next frontier in lipidology [1:44:45]; and
More.

Connect With Peter on Twitter, Instagram, Facebook and YouTube