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

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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
Volume43
Issue number5
Publication statusPublished - 01-01-2005

Fingerprint

Monocrotaline
pioglitazone
PPAR gamma
Pulmonary Hypertension
Ligands
Lung
troglitazone
Proliferating Cell Nuclear Antigen
Biotin
Vascular Smooth Muscle
Pulmonary Artery
Smooth Muscle Myocytes
Cell Proliferation
Apoptosis
Cytoplasmic and Nuclear Receptors
Blood Vessels
Pressure
Cell Line

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Matsuda, Yasushi ; Hoshikawa, Yasushi ; Ameshima, Shingo ; Suzuki, Satoshi ; Okada, Yoshinori ; Tabata, Toshiharu ; Sugawara, Takafumi ; Matsumura, Yuuji ; Kondo, Takashi. / Effects of peroxisome proliferator-activated receptor gamma ligands on monocrotaline-induced pulmonary hypertension in rats. In: Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 2005 ; Vol. 43, No. 5. pp. 283-288.
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Effects of peroxisome proliferator-activated receptor gamma ligands on monocrotaline-induced pulmonary hypertension in rats. / Matsuda, Yasushi; Hoshikawa, Yasushi; Ameshima, Shingo; Suzuki, Satoshi; Okada, Yoshinori; Tabata, Toshiharu; Sugawara, Takafumi; Matsumura, Yuuji; Kondo, Takashi.

In: Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society, Vol. 43, No. 5, 01.01.2005, p. 283-288.

Research output: Contribution to journalArticle

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AU - Hoshikawa, Yasushi

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