Upregulation of ALOX12−12-HETE pathway impairs AMPK-dependent modulation of vascular metabolism in ApoE/LDLR−/− mice
Mariola Olkowicz, Agnieszka Karaś, Piotr Berkowicz, Patrycja Kaczara, Agnieszka Jasztal, Zuzanna Kuryłowicz, Filip Fedak, Hernando Rosales-Solano, Kanchan Sinha Roy, Agnieszka Kij, Elżbieta Buczek, Janusz Pawliszyn, Stefan Chłopicki
Abstract
mice showed increased aortic expression of ALOX12, particularly in early atherosclerotic plaque areas. Remarkably, the joint blocking of ALOX12 and activation of AMPK, but not AMPK activation alone, resulted in the reprogramming of vascular metabolism, with improved mitochondrial respiration and suppressed auxiliary pathways (HBP, PPP, itaconate shunt). In conclusion, excessive activation of the ALOX12-12-HETE pathway in vascular inflammation in early atherosclerosis inhibits AMPK-dependent regulation of vascular metabolism. Consequently, ALOX12 may represent a novel target to boost impaired vascular mitochondrial function in pro-atherosclerotic vascular inflammation.