CEPT1-Mediated Phospholipogenesis Regulates Endothelial Cell Function and Ischemia-Induced Angiogenesis Through PPARα.
Abstract
De novo phospholipogenesis, mediated by choline-ethanolamine phosphotransferase 1 (CEPT1), is essential for phospholipid activation of transcription factors such as peroxisome proliferator-activated receptor α (PPARα) in the liver. Fenofibrate, a PPARα agonist and lipid-lowering agent, decreases amputation incidence in patients with diabetes. Because we previously observed that CEPT1 is elevated in carotid plaque of patients with diabetes, we evaluated the role of CEPT1 in peripheral arteries and PPARα phosphorylation (Ser12). CEPT1 was found to be elevated in diseased lower-extremity arterial intima of individuals with peripheral arterial disease and diabetes. To evaluate the role of Cept1 in the endothelium, we engineered a conditional endothelial cell (EC)-specific deletion of Cept1 via induced VE-cadherin-CreERT2-mediated recombination (Cept1Lp/LpCre +). Cept1Lp/LpCre + ECs demonstrated decreased proliferation, migration, and tubule formation, and Cept1Lp/LpCre + mice had reduced perfusion and angiogenesis in ischemic hind limbs. Peripheral ischemic recovery and PPARα signaling were further compromised by streptozotocin-induced diabetes and ameliorated by feeding fenofibrate. Cept1 endoribonuclease-prepared siRNA decreased ...Continue Reading
References
Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway
Related Concepts
Related Feeds
Cell Migration
Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.
American Diabetes Association Journals
Discover the latest diabetes research published by the journals from the American Diabetes Association.