Decreased surfactant proteins in lambs with pulmonary hypertension secondary to increased blood flow.
Infants with increased pulmonary blood flow secondary to congenital heart disease suffer from tachypnea, dyspnea, and recurrent pulmonary infections. We have recently established a model of pulmonary hypertension secondary to increased pulmonary blood flow in lambs after in utero placement of an aortopulmonary vascular graft. The purpose of the present study was to utilize our animal model to determine the effects on the expression of surfactant proteins A (SP-A), B (SP-B), and C (SP-C). At age 4 wk, SP-A mRNA content in lambs decreased to 61.4 +/- 8% of age-matched control value (n = 5; P < 0.05). In addition, SP-A protein content was decreased to 50 +/- 12% of control value (n = 6; P < 0.0001). Although we did not observe statistically significant changes in SP-B mRNA content, SP-B protein was decreased to 74 +/- 25% of control value (n = 4; P < 0.02). There was no difference in SP-C mRNA. These data show that in a model of congenital heart disease with pulmonary hypertension secondary to increased pulmonary blood flow, there is a decrease in SP-A gene expression as well as a decrease in SP-A and SP-B protein contents.
Gutierrez
J A
JA
Department of Pediatrics, University of California, San Francisco, California 94143, USA. jgut@itsa.ucsf.edu
Parry
A J
AJ
McMullan
D M
DM
Chapin
C J
CJ
Fineman
J R
JR
D000818:Animals; D000831:Animals, Newborn; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D006330:Heart Defects, Congenital / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008168:Lung / Q000378:metabolism*; D011247:Pregnancy; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism*; D011652:Pulmonary Circulation; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D014020:Tissue Extracts / Q000737:chemistry
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014020:Tissue Extracts