Effect of erythrophagocytosis-induced ferroptosis during angiogenesis in atherosclerotic plaques

• DOI: 10.1007/s10456-023-09877-6
• Publication Date: 2023-04-29T16:02:26Z
• Authors: Pauline Puylaert; Lynn Roth; Melissa Van Praet; Isabel Pintelon; Catalina Dumitrascu; Alexander van Nuijs; Greta Klejborowska; Pieter-Jan Guns; Tom Vanden Berghe; Koen Augustyns; Guido R. Y. De Meyer; Wim Martinet
• Keywords: Original Paper; Mice; Apolipoproteins E; Fibrillin-1; Ferritins; Oxygenases; Animals; Ferroptosis; Human medicine; Heme; Atherosclerosis; Plaque, Atherosclerotic; 3. Good health

Intraplaque (IP) angiogenesis is a key feature of advanced atherosclerotic plaques. Because IP vessels are fragile and leaky, erythrocytes released phagocytosed by macrophages (erythrophagocytosis), which leads to high intracellular iron content, lipid peroxidation cell death. In vitro experiments showed that erythrophagocytosis induced non-canonical ferroptosis, an emerging type regulated necrosis may contribute plaque destabilization. Erythrophagocytosis-induced ferroptosis was accompanied increased expression heme-oxygenase 1 ferritin, could be blocked co-treatment with third generation inhibitor UAMC-3203. Both ferritin were also expressed in erythrocyte-rich regions carotid plaques from ApoE-/- Fbn1C1039G+/- mice, model atherosclerosis angiogenesis. The effect UAMC-3203 (12.35 mg/kg/day) on evaluated mice fed western-type diet (WD) for 12 weeks (n = 13 mice/group) or 20 16-21 distinguish between without established angiogenesis, respectively. A significant decrease thickness observed after WD (87 ± 19 μm vs. 166 μm, p 0.006), particularly confirmed hemorrhage (108 35 322 40 0.004). This decreased expression. did not affect the aorta, typically do develop Altogether, erythrophagocytosis-induced during larger plaques, can prevented