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

A Csiszar, N Labinskyy, H Jo… - American Journal of …, 2008 - journals.physiology.org
A Csiszar, N Labinskyy, H Jo, P Ballabh, Z Ungvari
American Journal of Physiology-Heart and Circulatory Physiology, 2008journals.physiology.org
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 …
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 O2•− 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.
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