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Ferroptosis of smooth muscle cells in vascular diseases: from basic principles to clinical translation

Cell Death Discovery 2026
Yiqing Yang, Abdul Qadir Nawabi, Yuyu Yao, Naifeng Liu

Summary

Scientists have discovered that smooth muscle cells in blood vessels can die through a process called "ferroptosis" - a type of cell death caused by iron buildup and toxic fats. This review of existing research shows that this cell death process contributes to many serious heart and blood vessel diseases, including atherosclerosis, high blood pressure, and aneurysms. Understanding how this happens could lead to new treatments that protect blood vessels and reduce the risk of heart attacks and strokes.

Vascular smooth muscle cells (VSMCs), which form the media layer of blood vessels, play a vital role in vascular homeostasis and remodeling. Dysfunction of VSMCs represents a key pathological basis and an important contributor to vascular diseases. Ferroptosis, an iron-dependent accumulation of lipid hydroperoxides, is a novel form of regulated cell death. VSMC ferroptosis is involved in a range of vascular diseases, such as atherosclerosis, vascular calcification, hypertension, aortic aneurysm, aortic dissection, neointimal hyperplasia, intracranial aneurysm, and pulmonary arterial hypertension. This review summarizes the current evidence, underlying potential mechanisms, and therapeutic targets of VSMC ferroptosis in vascular diseases. A deeper understanding of this process may provide therapeutic insights and help in mitigating cardiovascular risk in affected patients.

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