Although physiological responses to chronic hypoxia, including pulmonary hypertension and right ventricular hypertrophy, have been well described, the molecular mechanisms involved in cardiopulmonary adaptations are still not fully understood. We hypothesize that adaptive responses to chronic hypoxia are the result of altered transcriptional regulations in the right and left ventricles. Here we report results from the gene expression profiling of adaptive responses in a chronically hypoxic heart. Of 11 analyzed candidate genes, the expression of seven and four genes, respectively, was significantly altered in the right ventricle of hypoxic male and female mice. In the transcriptional profile of the left ventricle, we identified a single expression change in hypoxic males (Vegfa gene). To directly test the role of HIF1, we analyzed the expression profile in Hif1a partially deficient mice exposed to moderate hypoxia. Our data showed that Hif1a partial deficiency significantly altered transcriptional profiles of analyzed genes in hypoxic hearts. The expression changes were only detected in two genes in the right ventricle of Hif1a(+/-) males and in one gene in the right ventricle of Hif1a(+/-) females. First, our results suggest that hypoxia mainly affects adaptive expression profiles in the right ventricle and that each ventricle can respond independently. Second, our findings indicate that HIF1a plays an important role in adaptive cardiopulmonary responses and the dysfunction of HIF1 pathways considerably affects transcriptional regulation in the heart. Third, our data reveal significant differences between males and females in cardiac adaptive responses to hypoxia and indicate the necessity of optimizing diagnostic and therapeutic procedures in clinical practice, with respect to sex.

Variants in the FTO (oxoglutarate‐dependent nucleic acid demethylase) gene have been associated with the BMI determination in Western European and North American populations. To widen the geographical coverage of the FTO studies, we have analyzed the association between the FTO gene variant rs17817449 (G>C) and obesity in a Slavic Eastern European population. A total of 3,079 males and 3,602 females 45–69 years old were randomly selected from population registers of seven Czech cities. We examined three indices of obesity: BMI (kg/m2), waist circumference, and waist‐to‐hip ratio (WHR). The FTO rs17817449 variant was significantly associated with BMI both in males (GG 28.7 ± 4.1; GT 28.3 ± 3.9; TT 28.0 ± 3.9; P = 0.003) and females (GG 28.7 ± 5.2; GT 28.2 ± 5.1; TT 27.2 ± 4.9; P < 0.001); the associations were not affected by adjustment for age, smoking, socioeconomic status, and physical activity. The FTO variant was also associated with waist circumference (difference between GG and TT was 1.1 cm (P = 0.043) in men and 2.4 cm (P < 0.001) in women) but this relationship disappeared after adjustment for BMI. Similarly, BMI explained the weak association of FTO with WHR and C‐reactive protein. FTO was not associated with plasma total and high‐density lipoprotein cholesterol, triglycerides, blood glucose, and blood pressure. These results confirm that in a Slavic population the FTO variant is strongly associated with BMI but not with other risk factors.

No abstract