Endothelial CEPT1 Promotes Angiogenesis Through PPARα and VEGF-A Signaling

作者：Tariq Jamal Khan, Rodrigo Meade, Santiago Elizondo Benedetto, Larisa Belaygorod, Omar Saffaf, Brigida Rusconi, Fong‐Fu Hsu, Sangeeta Adak, Batool Arif, Mohamed S. Zaghloul, Tiandao Li, Bo Zhang, Clay F. Semenkovich, Mohamed A. Zayed · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2025 · DOI：10.1161/atvbaha.125.323302 · 被引用次数：2 · 研究领域：Peroxisome Proliferator-Activated Receptors、Nitric Oxide and Endothelin Effects、Angiogenesis and VEGF in Cancer

BACKGROUND: Cept1 is essential for de novo phopholipogenesis and is impacted by diabetes. We previously demonstrated that conditional knockdown of Cept1 in the endothelium leads to reduced tissue recovery. Therefore, we hypothesized that Cept1 overexpression may also be sufficient in promoting postischemic angiogenesis and recovery in the setting of diabetes. METHODS: CEPT1 (choline-ethanolamine phosphotransferase 1) content was evaluated in the peripheral arteries of human patients with peripheral artery disease and with or without diabetes. We also engineered a conditional endothelial cell (EC)–specific Cept1 overexpression mouse ( Cept1 fl/fl Cre + ) in adult C57BL/6J (C57 black 6J) mice and performed unilateral hindlimb ischemia to assess the role of Cept1 in promoting angiogenesis. Murine aortae and ECs were harvested for single-cell RNA sequencing and molecular pathway analysis. RESULTS: In human arterial intima, CEPT1 was elevated in the setting of peripheral artery disease and diabetes, along with ACOX1 (acyl-coenzyme A oxidase 1), VEGF (vascular endothelial growth factor) R2, p-Akt (phosphorylated Akt), and p-eNOS (phosphorylated endothelial nitric oxide synthase). In mice, single-cell RNA sequencing demonstrated that ECs with Cept1 overexpression were enriched with wound healing, angiogenesis, sprouting, and cell migration pathways. Diabetic Cept1 fl/fl Cre + mice that underwent hindlimb ischemia demonstrated improved hindlimb perfusion and angiogenesis, and their a...