Foam Cells in Atherosclerosis: Novel Insights Into Its Origins, Consequences, and Molecular Mechanisms

This review goes under the hood of atherosclerosis to the cell that defines it: the foam cell, a lipid-engorged scavenger that is the building block of plaque. Understanding it explains why our therapies work — and where the next ones might come from.

A few insights stand out. Foam cells aren’t only macrophages; smooth-muscle cells contribute a large share — 30 to 70% in advanced plaque. Whether a cell becomes a foam cell comes down to a balance: cholesterol flowing in (via scavenger receptors like CD36) versus flowing out (via the transporters ABCA1 and ABCG1 to HDL). And how foam cells die — by several programmed pathways — feeds the necrotic core that makes plaque unstable. The review also flags newer regulators: microRNAs such as miR-33 that throttle cholesterol efflux, and the gut-derived molecule TMAO.

The practical relevance is explanatory rather than prescriptive. This biology is why lowering LDL shrinks plaque, why HDL’s cholesterol-removal role matters, and why inflammation is a target (consistent with the CANTOS trial). The honest status quo is that many of these elegant targets — including HDL-raising — have disappointed in trials.

We rate the evidence solid for a mechanistic review: comprehensive, peer-reviewed, well synthesized. Its clinical significance is moderate — it deepens understanding and points to future targets, but it is basic science that explains current practice rather than changing it.