How a microscopic injury leads to the world's leading cause of death

Science · Published 25 October 2026 Swipe more like this →

In short: Atherosclerosis isn't just about 'clogged pipes.' It is a complex, chronic inflammatory cascade that begins with a single microscopic event: endothelium activation. This biological chain reaction transforms healthy arteries into stiffened pathways, eventually triggering the most common cause of mortality globally.

The process begins with endothelial injury or activation—the initial trigger where the innermost lining of the artery becomes dysfunctional. Once activated, the endothelium allows for a cascade of events including lipid accumulation and the recruitment of inflammatory pathways. This leads to the formation of atheromas, which are plaques composed of fats, cholesterol, fibrous elements, and calcium deposits that narrow and stiffen the vessel walls.

A critical mechanism in this progression involves low-density lipoproteins (LDLs). These protein-lipid complexes deliver cholesterol into the arterial lining, where they are scavenged by immune cells called macrophages. When these macrophages become engorged with lipids, they transform into 'foam cells.' As these cells die and accumulate alongside cellular debris, smooth muscle cells, and minerals like calcium salts, tiny 'fatty streaks' can enlarge into substantial atherosclerotic plaques.

This progression is not merely a passive buildup; it is an active pathological process. Research highlights the vital role of inflammation, involving specific signaling cascades in macrophages and other leukocytes that promote plaque growth. Beyond traditional factors, modern science identifies non-traditional drivers such as disturbed sleep, physical inactivity, and even the microbiome as contributors to this global health burden.

The clinical stakes are high: when these plaques affect coronary arteries, they restrict oxygen-rich blood flow, causing angina pectoris (chest pain). If a plaque ruptures or causes complete occlusion, it can lead to myocardial infarction (heart attack) or stroke. Understanding these molecular and cellular mechanisms is essential for identifying new therapeutic targets to halt the progression of cardiovascular disease.

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