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. 2015 Jun 15;125(7):2759–2771. doi: 10.1172/JCI80369

Figure 3. Depletion of PHD2/3 exaggerates myocardial injury induced by chronic treatment with ISO.

Figure 3

(A) Short-term deletion of Phd2 and Phd3 had no significant effect on cardiac function. ECG analyses of Phd2/3fl/fl Cre+/– mice were performed 2 weeks after day 1 of i.p. injection of tamoxifen or corn oil control (n = 5/group). NS, 2-tailed Student’s t test. (B and C) Deletion of PHD2 and PHD3 exacerbated cardiac dysfunction induced by ISO in female mice. Female Phd2/3fl/fl Cre+/– and Phd2/3fl/fl Cre–/– mice were i.p. injected with tamoxifen once daily for 5 days, followed by PBS or ISO infusion with miniosmotic pumps (20 mg/kg/d) for 7 days, and cardiac function was measured by ECG. Quantitative analysis of fractional shortening is shown in B (n = 5/group). *P < 0.05, 2-way ANOVA. Representative M-mode ECGs of Phd2/3fl/fl Cre+/– and Phd2/3fl/fl Cre–/– mice after 7 days’ treatment with ISO are shown in C. (D and E) Survival of male Phd2- and Phd3-null mice was significantly lower than that of WT mice. Male Phd2/3fl/fl Cre+/– and Phd2/3fl/fl Cre–/– mice were i.p. injected with tamoxifen once daily for 5 days, followed by infusion of PBS or ISO for 7 days. Kaplan-Meier survival curves for mice with the indicated genotypes are shown in D. *P < 0.01, log-rank test. Representative ECGs with severe cardiac arrhythmias observed in male Phd2/3fl/fl Cre+/– mice are shown in E.