Effects of peroxisome proliferator-activated receptor gamma ligands on monocrotaline-induced pulmonary hypertension in rats

Yasushi Matsuda, Yasushi Hoshikawa, Shingo Ameshima, Satoshi Suzuki, Yoshinori Okada, Toshiharu Tabata, Takafumi Sugawara, Yuuji Matsumura, Takashi Kondo

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Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily, which regulates transcription of target genes in a ligand-dependent manner. Ligands for PPARgamma have been shown to attenuate proliferation of vascular smooth muscle cells, and to induce apoptosis in several cell lines in vitro. Since monocrotaline (MCT)-induced pulmonary hypertension in rats is characterized by proliferation of pulmonary vascular smooth muscle cells, we hypothesized that PPARgamma ligands may reduce MCT-induced pulmonary hypertension. To test this hypothesis, we treated MCT-injected rats with pioglitazone and troglitazone, synthetic ligands for PPARgamma, for three weeks and measured pulmonary artery pressure and pulmonary vessel wall thickness. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and immunostaining for proliferating cell nuclear antigen (PCNA) were utilized to assess apoptosis and cell proliferation in the pulmonary arterial walls of pioglitazone-treated rats. MCT with pioglitazone or troglitazone treatment significantly reduced pulmonary hypertension and wall thickening of the pulmonary arteries. TUNEL-positive apoptotic cells were not seen in the pulmonary arterial walls of either MCT-injected or control rats with or without pioglitazone. PCNA-positive cells were only seen in the thickened pulmonary arterial walls of MCT rats, but not in the pulmonary arterial walls of controls and of pioglitazone-treated MCT rats. We conclude that PPARgamma ligands reduce MCT-induced pulmonary hypertension and pulmonary vascular wall thickening in rats. Inhibition of MCT-induced cell proliferation in the pulmonary arterial walls may account for this effect

Original languageEnglish
Pages (from-to)283-288
Number of pages6
JournalNihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society
Issue number5
Publication statusPublished - 05-2005


All Science Journal Classification (ASJC) codes

  • Medicine(all)

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