Alterations in sheep fetal right ventricular tissue with induced hemodynamic pressure overload.
We report on the cellular and molecular effects of acute and chronic hemodynamic overload on the fetal sheep heart. In one fetus of a twin gestation, the pulmonary artery was banded to create a condition of hemodynamic pressure overload in the right ventricle. The effects of this overload on the right ventricle (RV), left ventricle (LV), and intra-ventricular septum (IVS) of the heart were studied and compared to that in a control, unbanded twin fetus. At the cellular level, the histological data showed that both the size of the nuclei and the overall cell size of cardiac myocytes were increased after five days of banding; although, with one hour of banding no effects were detected at the cellular level. Based on prior studies on connexins which showed their involvement in differentiation, remodeling, and response to load we looked at their expression in control and experimental hearts. At the molecular level, changes in expression of connexin isoforms, the main gap junction protein in the heart, were observed after both one hour and five days of banding. Changes were observed in expression of connexins 40, 43, and 45. For connexin 43 there was a significant reduction confined to the right ventricle, in the chronically treated fetus, whereas, connexins 40 and 45 expression decreased after acute overload. These early molecular changes are significant because the "functional syncytium" of the myocardium is established through the gap junction connections. Alterations in connexin isoform expression affect the development, mechanical, and electrophysiological properties of the heart muscle. These changes may contribute to the ultimate result of continued hemodynamic stress on the right ventricle: heart failure.
Temple Medical School, Department of Anatomy and Cell Biology, Philadelphia, PA 19140, USA. jll@astro.ocis.temple.edu
M O
MO
Montgomery
Y
Y
Jiao
S J
SJ
Phillips
G
G
Singh
J
J
Xu
R
R
Balsara
J
J
Litvin
D000818:Animals; D015152:Blotting, Northern; D017630:Connexins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005318:Fetal Heart / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D005500:Follow-Up Studies; D005865:Gestational Age; D006352:Heart Ventricles / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D006976:Hypertension, Pulmonary / Q000473:pathology* / Q000503:physiopathology; D009929:Organ Size; D011247:Pregnancy; D011669:Pulmonary Wedge Pressure; D012313:RNA / Q000096:biosynthesis; D012756:Sheep
D017630:Connexins; D012313:RNA