# Atherosclerosis

Atherosclerosis is the slow, inflammation-driven clogging of your medium and large arteries. It starts when cholesterol-carrying particles (ApoB-containing lipoproteins, mainly LDL) get trapped in the artery wall. That sets off a self-amplifying immune reaction that narrows and stiffens the vessel over time. Williams and Tabas (1995) called the trigger the 'response-to-retention' hypothesis: the ApoB100 particle sticks electrostatically to molecules in the artery wall. Once trapped, LDL gets chemically modified, which draws in immune cells (monocytes) that turn into macrophages and gorge on the fatty particles. Bloated with fat, they become 'foam cells', the signature of early streaks. Over decades these foam cells die and leave a greasy, dead core. Add migrating muscle cells and a fibrous cap, and you have a mature plaque. If an unstable plaque ruptures, it triggers a heart attack or stroke, which is why atherosclerosis is the world's leading cause of death. The role of LDL is nailed down by genetics (Mendelian randomization) and statin trials. The inflammation side was confirmed by the CANTOS trial (Ridker et al., 2017): blocking IL-1β with canakinumab cut cardiovascular events even without lowering LDL, proving inflammation is a fixable driver, not just a bystander.

## Sources

- Williams KJ, Tabas I. (1995). The Response-to-Retention Hypothesis of Early Atherogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/01.atv.15.5.551
- Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al.. (2017). Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa1707914
- La Chica Lhoëst MT, Martinez A, Claudi L, Garcia E, Benitez-Amaro A, Polishchuk A, et al.. (2024). Mechanisms modulating foam cell formation in the arterial intima: exploring new therapeutic opportunities in atherosclerosis. Frontiers in Cardiovascular Medicine. https://doi.org/10.3389/fcvm.2024.1381520

---

_Canonical: https://longevity-switzerland.com/en/glossary/atherosclerosis · Part of Longevity Cities · Updated 2026-06-22_