Differential proinflammatory and prooxidant effects of bone morphogenetic protein-4 in coronary and pulmonary arterial endothelial cells

Anna Csiszar, Nazar Labinskyy, Hanjoong Jo, Praveen Ballabh, Zoltan Ungvari

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

There is increasing evidence that TGF-β family member cytokine bone morphogenetic protein (BMP)-4 plays different pathophysiological roles in the pulmonary and systemic circulation. Upregulation of BMP-4 has been linked to atherosclerosis and hypertension in the systemic circulation, whereas disruption of BMP-4 signaling is associated with the development of pulmonary hypertension. To test the hypothesis that BMP-4 elicits differential effects in the pulmonary and systemic circulation, we compared the prooxidant and proinflammatory effects of BMP-4 in cultured human coronary arterial endothelial cells (CAECs) and pulmonary arterial endothelial cells (PAECs). We found that BMP-4 (from 0.3 to 10 ng/ml) in CAECs increased O2•- and H2O2 generation, induced NF-κB activation, upregulated ICAM-1, and induced monocyte adhesiveness to ECs. In contrast, BMP-4 failed to induce oxidative stress or endothelial activation in PAECs. Also, BMP-4 treatment impaired acetylcholine-induced relaxation and increased O 2•- production in cultured rat carotid arteries, whereas cultured rat pulmonary arteries were protected from these adverse effects of BMP-4. Thus, we propose that BMP-4 exerts prooxidant, prohypertensive, and proinflammatory effects only in the systemic circulation, whereas pulmonary arteries are protected from these adverse effects of BMP-4. The vascular bed-specific endothelial effects of BMP-4 are likely to contribute to its differential pathophysiological role in the systemic and pulmonary circulation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number2
DOIs
StatePublished - Aug 2008
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 4
Endothelial Cells
Lung
Pulmonary Circulation
Pulmonary Artery
Adhesiveness
Intercellular Adhesion Molecule-1
Carotid Arteries
Pulmonary Hypertension
Acetylcholine
Blood Vessels
Monocytes

Keywords

  • Endothelial dysfunction
  • Oxidative stress
  • Pulmonary
  • Systemic

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Differential proinflammatory and prooxidant effects of bone morphogenetic protein-4 in coronary and pulmonary arterial endothelial cells. / Csiszar, Anna; Labinskyy, Nazar; Jo, Hanjoong; Ballabh, Praveen; Ungvari, Zoltan.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 295, No. 2, 08.2008.

Research output: Contribution to journalArticle

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