TY - JOUR
T1 - Longitudinal transcriptional analysis of developing neointimal vascular occlusion and pulmonary hypertension in rats
AU - Vaszar, Laszlo T.
AU - Nishimura, Toshihiko
AU - Storey, John D.
AU - Zhao, Guohua
AU - Qiu, Daoming
AU - Faul, John L.
AU - Pearl, Ronald G.
AU - Kao, Peter N.
PY - 2004/7
Y1 - 2004/7
N2 - Pneumonectomized rats injected with the alkaloid toxin, monocrotaline, develop progressive neointimal pulmonary vascular obliteration and pulmonary hypertension resulting in right ventricular failure and death. The antiproliferative immunosuppressant, triptolide, attenuates neointimal formation and pulmonary hypertension in this disease model (Faul JL, Nishimura T, Berry GJ, Benson GV, Pearl RG, and Kao PN. Am J Respir Crit Care Med 162: 2252-2258, 2000). Pneumonectomized rats, injected with monocrotaline on day 7, were killed at days 14, 21, 28, and 35 for measurements of physiology and gene expression patterns. These data were compared with pneumonectomized, monocrotaline-injected animals that received triptolide from day 5 to day 35. The hypothesis was tested that a group of functionally related genes would be significantly coexpressed during the development of disease and downregulated in response to treatment. Transcriptional analysis using total lung RNA was performed on replicate animals for each experimental time point with exploratory data analysis followed by statistical significance analysis. Marked, statistically significant increases in proteases (particularly derived from mast cells) were noted that parallel the development of vascular obliteration and pulmonary hypertension. Mast-cell-derived proteases may play a role in regulating the development of neointimal pulmonary vascular occlusion and pulmonary hypertension in response to injury.
AB - Pneumonectomized rats injected with the alkaloid toxin, monocrotaline, develop progressive neointimal pulmonary vascular obliteration and pulmonary hypertension resulting in right ventricular failure and death. The antiproliferative immunosuppressant, triptolide, attenuates neointimal formation and pulmonary hypertension in this disease model (Faul JL, Nishimura T, Berry GJ, Benson GV, Pearl RG, and Kao PN. Am J Respir Crit Care Med 162: 2252-2258, 2000). Pneumonectomized rats, injected with monocrotaline on day 7, were killed at days 14, 21, 28, and 35 for measurements of physiology and gene expression patterns. These data were compared with pneumonectomized, monocrotaline-injected animals that received triptolide from day 5 to day 35. The hypothesis was tested that a group of functionally related genes would be significantly coexpressed during the development of disease and downregulated in response to treatment. Transcriptional analysis using total lung RNA was performed on replicate animals for each experimental time point with exploratory data analysis followed by statistical significance analysis. Marked, statistically significant increases in proteases (particularly derived from mast cells) were noted that parallel the development of vascular obliteration and pulmonary hypertension. Mast-cell-derived proteases may play a role in regulating the development of neointimal pulmonary vascular occlusion and pulmonary hypertension in response to injury.
KW - Gene expression analysis
KW - Mast cells
KW - Monocrotaline
KW - Proteinases
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U2 - 10.1152/physiolgenomics.00198.2003
DO - 10.1152/physiolgenomics.00198.2003
M3 - Article
C2 - 15082832
AN - SCOPUS:3142722666
SN - 1531-2267
VL - 17
SP - 150
EP - 156
JO - Physiological Genomics
JF - Physiological Genomics
ER -