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Am J Physiol Heart Circ Physiol (May 23, 2008). doi:10.1152/ajpheart.01272.2007
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Submitted on October 31, 2007
Accepted on May 20, 2008

Maternal undernutrition induces differential cardiac gene expression in pulmonary hypertensive steers at high elevation

Hyungchul Han1*, Thomas R Hansen2, Brynn Berg3, Bret W Hess3, and Stephen P. Ford4

1 Animal Sciences, Colorado State University, Fort Collins, Colorado, United States
2 Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States
3 Animal Science, University of Wyoming, Laramie, Wyoming, United States
4 Department of Animal Science, University of Wyoming, Laramie, Wyoming, United States

* To whom correspondence should be addressed. E-mail: hyungchul.han{at}colostate.edu.

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 (2183 m). On day 30 of gestation, forty AngusXGelbvieh 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 40-114 mmHg was determined in 15-mo-old steers from Control or Restricted cows prior to 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 &#947; coactivator 1&#945; were differentially expressed (P<0.05) in steer right ventricle from high PAP cows compared to low PAP cows. Also, activation peptide and pancreas cationic trypsinogen, &#945; actin and similar to ubiquitin carboxylesterase were differently expressed (P<0.05) in steers from restricted cows when compared to those from control cows. Upregulated genes in high PAP RV 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.







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