The mitochondrial respiratory chain inhibitor rotenone reduces aortic adventitial Msx2 expression in vitro and in vivo. A, Rotenone inhibits TNF induction of Msx2-Wnt signaling in primary aortic myofibroblast cultures (n = 6 per treatment). Msx1 and GAPDH (glyceraldehyde phosphate dehydrogenase) were not altered. Rotenone treatment was initiated 30 min before challenge with TNF. B, Conversely, pyruvic acid, an anapleurotic substrate for mitochondrial tricarboxylic cycle metabolism, significantly enhances TNF induction of Msx2 (n = 6 per treatment). C, In vivo rotenone treatment reduces aortic Msx2, but not Msx1, in SM22-TNF transgenic mice (n = 16 animals per treatment group).