Rous Whipple Award Lecture. Atherosclerosis A Defense Mechanism Gone Awry

This landmark research presents a groundbreaking way of understanding atherosclerosis - the buildup of plaque in arteries that leads to heart attacks, strokes, and other serious health problems. Rather than viewing atherosclerosis as simply a accumulation of cholesterol and debris in blood vessels, Dr. Russell Ross proposes that it's actually the result of the body's protective mechanisms working too hard for too long.

The "response-to-injury hypothesis" explains that when artery walls are damaged by factors like high blood pressure, smoking, or inflammatory substances, the body naturally responds by sending immune cells to the site to heal and protect the area. White blood cells called monocytes stick to the damaged artery walls and transform into macrophages, while T-cells (another type of immune cell) also join the response. These cells release various signaling molecules and growth factors as part of the healing process.

The problem occurs when this protective response becomes chronic and excessive. Instead of healing the artery and stopping, the inflammatory process continues indefinitely. The immune cells keep releasing growth factors that cause smooth muscle cells in the artery wall to multiply and migrate, eventually forming the thick, dangerous plaques that can block blood flow or rupture and cause heart attacks.

This research fundamentally changed how we understand cardiovascular disease by showing it's primarily an inflammatory condition rather than just a plumbing problem. In clinical practice, this insight has led to treatments that target inflammation alongside cholesterol management, and helps explain why lifestyle factors that reduce chronic inflammation - like regular exercise, stress management, and anti-inflammatory diets - are so crucial for heart health and longevity.