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Am J Physiol Heart Circ Physiol 295: H382-H389, 2008. First published May 23, 2008; doi:10.1152/ajpheart.01272.2007
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Maternal undernutrition induces differential cardiac gene expression in pulmonary hypertensive steers at high elevation

Hyungchul Han,1,2,3 Thomas R. Hansen,4 Brynn Berg,1,2 Bret W. Hess,1,2 and Stephen P. Ford1,2

1Center for the Study of Fetal Programming and 2Department of Animal Science, University of Wyoming, Laramie, Wyoming; Departments of 3Animal Sciences and 4Biomedical Sciences, Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort Collins, Colorado

Submitted 31 October 2007 ; accepted in final form 20 May 2008

Pulmonary hypertension, characterized by elevated pulmonary arterial pressure (PAP) and right ventricular hypertrophy, is caused by decreased atmospheric oxygen at high altitude. We hypothesized that maternal undernutrition programs right ventricle gene expression and sensitivity to increasing PAP at high altitude (2,183 m). On day 30 of gestation, forty Angus x Gelbvieh cows received diets to induce either gain (Control) or loss of body weight (Restricted) until day 125 of gestation. On day 126 of gestation, Restricted cows were realimented to achieve the same body weight as Controls by day 250. Parturition occurred naturally. PAP, which ranged from 40 to 114 mmHg, was determined in 15-mo-old steers from Control or Restricted cows before necropsy. At necropsy, hearts were collected from steers, separated into right and left ventricles, atria, and septa and weighed. Ventricular thickness was recorded. Eight Affymetrix bovine microarrays were screened [four high PAP (two Control and two Restricted) and four low PAP (two Control and two Restricted)] with right ventricle mRNA. This analysis revealed that pentraxin-related protein, interferon-related developmental regulator, and peroxisome proliferator-activated receptor-{gamma} coactivator-1{alpha} were differentially expressed (P < 0.05) in steer right ventricle from high-PAP cows compared with low-PAP cows. Also, activation peptide and pancreas cationic trypsinogen, {alpha}-actin, similar to ubiquitin carboxylesterase, were differently expressed (P < 0.05) in steers from Restricted cows compared with those from Control cows. Upregulated genes in high-PAP right ventricle have been associated with pathological cardiac hypertrophy. It is concluded that right ventricle gene expression may be differentially programmed by maternal undernutrition in the fetus during early gestation and may be detrimental to health and longevity of offspring, particularly at high altitude.

right ventricle; high altitude



Address for reprint requests and other correspondence: H. Han, Dept. of Animal Sciences, Colorado State Univ., Fort Collins, CO 80523 (e-mail: hyungchul.han{at}colostate.edu)







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