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. Author manuscript; available in PMC: 2018 Oct 1.
Published in final edited form as: Circ Cardiovasc Genet. 2017 Oct;10(5):e001706. doi: 10.1161/CIRCGENETICS.117.001706

Figure 3.

Figure 3

Effect of chronic hypoxia on heart function in hearts with myocardial and pericardial knockdown of calcineurins. A, left, Protocol for chronic hypoxia assay. B–G, Heart function data under normoxia (left bars) or CH exposure (right bars) per genotypes indicated in figure key (A, right): progeny of CanA14F-RNAi and Pp2B-RNAi crossed to a Hand4.2-Gal4 driver causes knockdown (KD) specifically in pericardial and myocardial cells during development through adulthood. Hearts were dissected and assayed under 21% O2 after 3 weeks at 21% or 4% O2 (as in Zarndt et al20). Note that cardiac Pp2B-RNAi KD flies under CH did not survive to 3 weeks. B, Heart period (HP) was reduced on cardiac Pp2B-RNAi KD in normoxia (condition: F=14.24, P=0.0002; genotype: F=8.089, P=0.0004; interaction=2.7, P=0.07). CanA14F KD had a similar put less pronounced effect. Under hypoxia, CanA14F KD had no significant effect. C, Similarly, diastolic intervals (DI) were reduced on cardiac CanA14F-RNAi and Pp2B-RNAi KD under normoxia, but not under CH (DI condition: F=13, P=0.0004; genotype: F=3.8, P=0.025; interaction =2.1, P=0.13). D, Systolic intervals (SI) were significantly elevated only in cardiac CanA14F KD flies after CH compared with controls under hypoxia (SI condition: F=0.64, P=0.43; genotype: F=7.8, P=0.0006; interaction =1.2, P=0.31). E, Fractional shortening (FS) was not significantly changed on cardiac calcineurin KD in normoxic flies. However, under hypoxia controls, CanA14F-RNAi KD in the heart results in reduced FS after CH (condition: F=0.53, P=0.47; genotype: F=20, P<0.0001; interaction=9.0, P=0.0002). F, Diastolic diameters were decreased significantly with both cardiac CanA14F-RNAi and PP2B-RNAi KD at normoxia, as well as with CanA14F KD under CH (condition: F=7.3, P=0.0009; genotype: F=14, P=0.0003; interaction=7.3, P=0.0009). G, Systolic diameters were similarly decreased with CanA14F and Pp2B KD at normoxia, as well as CanA14F KD under CH (condition: F=11, P=0.0009; genotype: F=1.4, P=0.26; interaction=F=3.0, P=0.055). All values are mean ± SEM (normoxia: N=37 KK control, N=33 CanA14F-RNAi, N=32 Pp2B-RNAi; chronic hypoxia: N=43 KK control, N=20 CanA14F-RNAi, N=20 Pp2B-RNAi). Two-way analysis of variance (ANOVA) and Sidak or Dunn multiple comparisons tests; *<0.05, **P<0.01, ***P<0.001. See also Materials and Methods.