Longitudinal transcriptional analysis of developing neointimal vascular occlusion and pulmonary hypertension in rats

Laszlo Vaszar, Toshihiko Nishimura, John D. Storey, Guohua Zhao, Daoming Qiu, John L. Faul, Ronald G. Pearl, Peter N. Kao

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalPhysiological Genomics
Volume17
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

Fingerprint

Monocrotaline
Pulmonary Hypertension
Blood Vessels
Mast Cells
Lung
Peptide Hydrolases
Statistical Data Interpretation
Immunosuppressive Agents
Alkaloids
Fruit
Down-Regulation
RNA
Gene Expression
Wounds and Injuries
Genes
triptolide

Keywords

  • Gene expression analysis
  • Mast cells
  • Monocrotaline
  • Proteinases

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Longitudinal transcriptional analysis of developing neointimal vascular occlusion and pulmonary hypertension in rats. / Vaszar, Laszlo; Nishimura, Toshihiko; Storey, John D.; Zhao, Guohua; Qiu, Daoming; Faul, John L.; Pearl, Ronald G.; Kao, Peter N.

In: Physiological Genomics, Vol. 17, 01.07.2004, p. 150-156.

Research output: Contribution to journalArticle

Vaszar, Laszlo ; Nishimura, Toshihiko ; Storey, John D. ; Zhao, Guohua ; Qiu, Daoming ; Faul, John L. ; Pearl, Ronald G. ; Kao, Peter N. / Longitudinal transcriptional analysis of developing neointimal vascular occlusion and pulmonary hypertension in rats. In: Physiological Genomics. 2004 ; Vol. 17. pp. 150-156.
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