Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells

Shen Zhang, Ivana Fantozzi, Donna D. Tigno, Eunhee S. Yi, Oleksandr Platoshyn, Patricia A. Thistlethwaite, Jolene M. Kriett, Gordon Yung, Lewis J. Rubin, Jason X J Yuan

Research output: Contribution to journalArticle

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Abstract

Pulmonary vascular medial hypertrophy in primary pulmonary hypertension (PPH) is mainly caused by increased proliferation and decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs). Mutations of the bone morphogenetic protein (BMP) receptor type II (BMP-RII) gene have been implicated in patients with familial and sporadic PPH. The objective of this study was to elucidate the apoptotic effects of BMPs on normal human PASMCs and to examine whether BMP-induced effects are altered in PASMCs from PPH patients. Using RT-PCR, we detected six isoforms of BMPs (BMP-1 through -6) and three subunits of BMP receptors (BMP-RIa, -RIb, and -RII) in PASMCs. Treatment of normal PASMCs with BMP-2 or -7 (100-200 nM, 24-48 h) markedly increased the percentage of cells undergoing apoptosis. The BMP-2-mediated apoptosis in normal PASMCs was associated with a transient activation or phosphorylation of Smad1 and a marked downregulation of the antiapoptotic protein Bcl-2. In PASMCs from PPH patients, the BMP-2- or BMP-7-induced apoptosis was significantly inhibited compared with PASMCs from patients with secondary pulmonary hypertension. These results suggest that the antiproliferative effect of BMPs is partially due to induction of PASMC apoptosis, which serves as a critical mechanism to maintain normal cell number in the pulmonary vasculature. Inhibition of BMP-induced PASMC apoptosis in PPH patients may play an important role in the development of pulmonary vascular medial hypertrophy in these patients.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume285
Issue number3 29-3
StatePublished - Sep 1 2003
Externally publishedYes

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Bone Morphogenetic Proteins
Vascular Smooth Muscle
Pulmonary Artery
Smooth Muscle Myocytes
Apoptosis
Lung
Bone Morphogenetic Protein 2
Hypertrophy
Blood Vessels
Bone Morphogenetic Protein 1
Type II Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein 7
Pulmonary Hypertension
Protein Isoforms
Down-Regulation
Cell Count
Phosphorylation
Familial Primary Pulmonary Hypertension
Polymerase Chain Reaction

Keywords

  • Arteries
  • Bcl
  • Hypertension
  • Smad
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Zhang, S., Fantozzi, I., Tigno, D. D., Yi, E. S., Platoshyn, O., Thistlethwaite, P. A., ... Yuan, J. X. J. (2003). Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells. American Journal of Physiology - Lung Cellular and Molecular Physiology, 285(3 29-3).

Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells. / Zhang, Shen; Fantozzi, Ivana; Tigno, Donna D.; Yi, Eunhee S.; Platoshyn, Oleksandr; Thistlethwaite, Patricia A.; Kriett, Jolene M.; Yung, Gordon; Rubin, Lewis J.; Yuan, Jason X J.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 285, No. 3 29-3, 01.09.2003.

Research output: Contribution to journalArticle

Zhang, S, Fantozzi, I, Tigno, DD, Yi, ES, Platoshyn, O, Thistlethwaite, PA, Kriett, JM, Yung, G, Rubin, LJ & Yuan, JXJ 2003, 'Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 285, no. 3 29-3.
Zhang, Shen ; Fantozzi, Ivana ; Tigno, Donna D. ; Yi, Eunhee S. ; Platoshyn, Oleksandr ; Thistlethwaite, Patricia A. ; Kriett, Jolene M. ; Yung, Gordon ; Rubin, Lewis J. ; Yuan, Jason X J. / Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2003 ; Vol. 285, No. 3 29-3.
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