Cigarette Smoke Extract Induces Ferroptosis in Vascular Smooth Muscle Cells.

Cigarette Smoke Extract Induces Ferroptosis in Vascular Smooth Muscle Cells. Am J Physiol Heart Circ Physiol. 2020 Jan 24;: Authors: Sampilvanjil A, Karasawa T, Yamada N, Komada T, Higashi T, Baatarjav C, Watanabe S, Kamata R, Ohno N, Takahashi M Abstract Cigarette smoking is a major risk factor for aortic aneurysm and dissection; however, no causative link between smoking and these aortic disorders has been proven. In the present study, we investigated the mechanism by which cigarette smoke affects vascular wall cells and found that cigarette smoke extract (CSE) induced a novel form of regulated cell death termed ferroptosis in VSMCs. CSE markedly induced cell death in A7r5 cells and primary rat VSMCs, but not in endothelial cells, which was completely inhibited by specific ferroptosis inhibitors (Ferrostatin-1 [Fer-1] and Liproxstatin-1) and an iron chelator (deferoxamine). CSE-induced VSMC death was partially inhibited by a GSH precursor (N-acetyl cysteine) and NADPH oxidase inhibitor (DPI), but not by inhibitors of pan-caspases (Z-VAD), caspase-1 (Z-YVAD), or necroptosis (Necrostatin-1). CSE also upregulated IL-1β, IL-6, TNF-α, MMP-2, MMP-9, and TIMP-1 in A7r5 cells, which was inhibited by Fer-1. Furthermore, CSE induced the upregulation of Ptgs2 mRNA, lipid peroxidation, and intracellular GSH depletion, which are key features of ferroptosis. VSMC ferroptosis was induced by acrolein and methyl vinyl ketone, major constituents o...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research