Itaconic acid induces angiogenesis and suppresses apoptosis via Nrf2/autophagy to prolong the survival of multi-territory perforator flaps

• DOI: 10.1016/j.heliyon.2023.e17909
• Publication Date: 2023-07-01T15:46:51Z
• Authors: Gaojie Luo; Zekun Zhou; Chengxiong Huang; Peiyao Zhang; Nianzhe Sun; Wei Chen; Chao Deng; Xiaoxiao Li; Panfeng Wu; Juyu Tang; Liming Qing
• Keywords: Itaconic acid

BackgroundPerforator flaps are widely used in hand microsurgery to reconstruct and repair soft tissue injuries. However, ischemia subsequent ischemia-reperfusion injury may cause distal necrosis of the flap. Itaconic acid (IA) is a modulator macrophage function, which exerts anti-inflammatory effects activation.MethodsThe necrotic area flap was detected by measuring temperature with an infrared thermometer. Flap cell apoptosis TUNEL staining Western blot analysis apoptosis-associated proteins Bcl-2 Bax. HE detect angiogenesis skin flaps. CD31 identify positive vascular expression, survival choke vessels different areas assessed arteriography. In addition, performed quantify expressions VEGF, Nrf2, LC3II, SQSTM1, CTSD.ResultsItaconic raises VEGF protein levels number CD31-positive vessels. The IA treatment group exhibited higher neovascularization less than those control group. results revealed that attenuated ischemic combination itaconic Nrf2 inhibitor ML385 reversed this beneficial effect. apoptosis, enhanced angiogenesis, autophagy.ConclusionIn summary, our findings indicate might be effective reduce necrosis. Additionally, study identified novel mechanism for on survival.