Figure 6. Fibroblast-specific TREK-1 loss of function protects against pressure overload–induced cardiac dysfunction.

(A) Conditional TREK-1 targeting strategy schematic: Frt sites flank a neomycin cassette and LoxP sites flank the conditional KO region. The conditional KO allele was obtained after Flp-mediated removal of the neomycin selection marker. (B) Serial echocardiographic measurements of average FS, (C) ESD, and (D) EDD in Kcnk2^fl/fl alone (Cre negative), aMHC-cre;Kcnk2^fl/fl (cardiomyocyte specific), and tcf21-iCre;Kcnk2^fl/fl (fibroblast specific) mice up to 8 weeks after TAC. Error bars reflect SEM. Data were compared using 2-way repeated measures ANOVA. P values for the interaction between genotype and weeks after TAC are shown adjacent to brackets. Comparisons between genotypes at each time point were made using Bonferroni’s test for multiple comparisons. ^†P < 0.05 versus Kcnk2^fl/fl; *P < 0.05 versus aMHC-cre;Kcnk2^fl/fl. (E) Tissue fibrosis quantified after 12 weeks of TAC in Kcnk2^fl/fl (sham = 3, TAC = 13 mice), aMHC-cre-cre;Kcnk2^fl/fl (TAC = 5 mice), and tcf21-iCre;Kcnk2^fl/fl (n = 9 mice) mice using Masson’s trichrome stain. (F) Representative histological sections showing fibrosis in purple. Comparisons between genotypes were made by Kruskal-Wallis test with uncorrected Dunn’s multiple comparisons test. *P < 0.05 versus Kcnk2^fl/fl sham; ^†P < 0.05 versus Kcnk2^fl/fl TAC; ^‡P < 0.05 versus aMHC-cre;Kcnk2^fl/fl.