LDL cholesterol moves through a blood vein (Image source: wikimedia commons.)

In the early 1970s in Dallas, Drs. Joseph Goldstein and Michael Brown began a fruitful and decades-long collaboration that ended up transforming our understanding of heart disease. The story revolves around low-density lipoprotein (LDL), a particle of lipids and proteins that transports cholesterol around our bodies. Goldstein, Brown, and their team discovered that human cells rely on a specialized type of sensor, called an LDL receptor, to remove LDL from the blood. While cholesterol is an essential building block of many body processes, without properly functioning receptors, LDL accumulates, clogging arteries and increasing the risk of heart attacks. Working with cells from patients who lacked the gene to make LDL receptors, the team learned that the function of these receptors was critical for removing excess cholesterol from the blood circulating through the body. This understanding was a stepping stone for the development of life-saving cholesterol-lowering drugs. For example, statins, which are one type of those widely used drugs, work by lowering circulating LDL. Goldstein and Brown’s findings were so pivotal that they earned the Nobel Prize in Physiology or Medicine in 1985.

But how did the team know to care about cholesterol in the first place? In 1948, the National Heart Institute (now the National Heart, Lung, and Blood Institute, or NHLBI) launched the Framingham Heart Study in Massachusetts. This large, very long-term study followed thousands of participants over decades, allowing the scientists to discern patterns that emerge only over the long term. The Framingham Heart Study introduced the concept of “risk factors.” One of their key findings was identifying high blood cholesterol as a major risk factor for heart disease. This was the impetus that led Goldstein and Brown to focus on cholesterol. The Framingham Heart Study refined our understanding of “good” and “bad” cholesterol, and more broadly, laid the foundation for modern preventive cardiology.

Thanks to decades of work into the fundamental understanding of cholesterol metabolism, knowledge that began in Framingham, Massachusetts found its way to a lab in Dallas, Texas and became a cornerstone of cardiovascular medicine—drastically reducing deaths from coronary artery disease, the world’s leading killer.