Laura Padrón-Barthe et al. JACC 2018;71:

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Laura Padrón-Barthe et al. JACC 2018;71:654-667 CnAβ1 Activates the Serine and One-Carbon Metabolic Pathway Without Interfering With NFAT-Mediated Transcription Expression of the Rcan1.4 (A) and Rcan1.1 (B) mRNA was analyzed by qRT-PCR 21 days after TAC. (C) WT and αMHC-CnAβ1 mice were crossed with reporter mice in which luciferase expression is controlled by an NFAT binding site multimer. Luciferase activity normalized to total protein content was analyzed in heart extracts 21 days post-TAC. (D) Summary of genes involved in the serine and one-carbon pathway. Components induced in αMHC-CnAβ1 mice are indicated by a blue fill (mRNA, metabolites) or purple border (protein). Expression of Phgdh (E), Psat1 (F), Shmt2 (G), Mthfd2 (H), and Aldh1l2 (I) was quantified as in (A). Values express average ± SEM. *p < 0.05, **p < 0.01 TAC versus sham for each mouse line; †p < 0.05, ††p < 0.01, †††p < 0.005 WT versus transgenic mice; 2-way analysis of variance plus Bonferroni post-test. n = 10 to 15 (A, B, and E–I); n = 5 to 12 (C). 3PG = 3-phosphoglycerate; 3P-Ser = 3-phosphoserine; Gly = glycine; NAD(P) = nicotinamide adenine dinucleotide phosphate; NAD(P)H = nicotinamide adenine dinucleotide phosphate (reduced form); NFAT = nuclear factor of activated T cells; qRT-PCR = quantitative reverse-transcription real-time polymerase chain reaction; Ser = serine; THF = tetrahydrofolate; other abbreviations as in Figure 1. Laura Padrón-Barthe et al. JACC 2018;71:654-667 2018 The Authors