Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats
J. Clin. Invest. Warner S. Simonides, et al. 118:975 doi:10.1172/JCI32824 [Go to this article.]

Figure 4
HIF-1α and D3 are selectively induced in the RV in a rat model of monocrotaline-induced RV hypertrophy. Thickening of the RV wall (A) and increased RV weight (B) were observed as CHF developed after monocrotaline administration. Values are mean ± SEM of 11–16 animals per group. (C–F) Western blot analysis of HIF-1α (C) and HIF-2α protein (D), D3 activity (E), and quantitative real-time PCR of D3 mRNA (F) in tissue prepared from the RV and LV of rats administered monocrotaline (CHF) versus saline control (CON). The HIF-2α Western blot in D depicts RV samples from control and CHF animals, with extracts of primary microvascular endothelial cells obtained from human foreskin and cultured under hypoxic conditions (1% O₂) serving as a positive control (+). Values are mean ± SEM of 3–9 animals per group. (F) D3 mRNA is expressed as the RV/LV ratio and shown as the relative fold change from the saline control group. *P < 0.05 versus control; **P < 0.05 versus LV; ***P < 0.005 versus control. (G) Myocardial reporter activity after in vivo cardiomyocyte transfection of the pLuc-TRE T3-responsive Firefly luciferase reporter, normalized to the expression of the pRen-C transfection control. Values are mean ± SEM of 5–29 animals per group. LV and RV reporter activity is shown in CHF versus control animals. In control animals with systemic hypothyroidism (Hypo), euthyroidism (Eu), or thyrotoxicosis from T3 treatment (Hyper), reporter levels from pooled LV/RV homogenates are shown. *P < 0.05 versus euthyroidism or hypothyroidism, ANOVA; **P < 0.05 versus control and LV.