An eleven-year-old girl, cholesterol-fed rabbits, a wartime centrifuge, and the receptors that transformed our understanding of heart disease.

In this episode, we trace how scientists uncovered the connection between cholesterol and atherosclerosis. We begin with an 1889 case involving a young girl covered in xanthomas, then follow cholesterol from its discovery in bile to the fatty plaques found inside diseased arteries.

From there, we explore the experiments that showed cholesterol could cause atherosclerosis, the technology that separated HDL from LDL, and the families whose early heart disease revealed the genetics of familial hypercholesterolemia. Finally, we examine the discovery of the LDL receptor and how it transformed our understanding of cholesterol metabolism laying the foundation for modern cholesterol-lowering therapies.

• (00:00:00) - Cholesterol: Xanthomas, Blood, and Bile
• (00:01:07) - The First Case of Familial Hypercholesterolemia
• (00:02:49) - What Is Cholesterol?
• (00:03:54) - From Hardening Arteries to Atherosclerosis
• (00:04:47) - Cholesterol’s Discovery in Bile
• (00:08:04) - Finding Cholesterol in Arterial Plaques
• (00:11:12) - Proving the Connection with Rabbits
• (00:14:25) - High Cholesterol Runs in Families
• (00:15:47) - Cholesterol Is More Than One Thing
• (00:17:37) - Discovering HDL and LDL
• (00:19:01) - Connecting LDL to Heart Disease
• (00:21:41) - The Discovery of the LDL Receptor