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. Author manuscript; available in PMC: 2017 May 27.
Published in final edited form as: Circ Res. 2016 May 27;118(11):1808–1829. doi: 10.1161/CIRCRESAHA.116.306923

Figure 4. Increased mitochondrial oxidation of glucose or fatty acids activates NFAT-mediated transcription of genes promoting diabetic atherosclerosis and heart failure.

Figure 4

Mitochondrial overproduction of ROS causes increased intracellular Ca++, which activates the calcium-activated neutral cysteine protease calpain. Calpain then activates the Ca2+/calmodulin-dependent /CaM) (Ca2+)serine/threonine phosphatase calcineurin. Dephosphorylation facilitates nuclear translocation of the transcription factor Nuclear Factor of Activated T Cells (NFAT). In the nucleus, NFAT interacts with polyADP-ribose polymerase (PARP), which increases NFAT transcriptional activity via NFAT polyADP ribosylation. MCP-1, monocyte chemoattractant protein-1; ICAM-1, Intercellular Adhesion Molecule 1; IL-6, Interleukin-6.