Effects of bone morphogenic proteins and transforming growth factor-beta on In-vitro production of endothelin-1 by human pulmonary microvascular endothelial cells

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Abstract

Background: Altered endothelial cell (EC)-derived mediator levels, including increased endothelin-1 (ET-1), are hallmarks of human pulmonary arterial hypertension (PAH). Gene mutations for receptors for bone morphogenic proteins (BMP), or transforming growth factor-β (TGF-β) cause heritable PAH. The effects of BMPs and TGF-β on ET-1 production by human pulmonary microvascular EC (HMVEC-LBl) are unknown. Methods: HMVEC-LBl were exposed in-vitro to BMPs 2, 4, and 7 or TGF-β1 in basal or complete medium. ET production was measured, as well as total cellular protein. Levels of Smad 5 and phosphorylated Smads 1/5 were also measured. Results: BMP-4 did not increase ET-1 while BMP-2 increased it minimally in basal medium. BMP-7 increased ET-1, but only at 100 ng/ml. By contrast, TGF-β increased ET-1 throughout most of the studied dose range. All BMPs and TGF-β increased levels of phosphorylated Smads 1/5 without depleting levels of Smad 5. Conclusions: With the exception of BMP-7 at high-concentrations, the BMPs that interact with BMP receptor 2, the receptor implicated in heritable PAH, do not or minimally modulate in-vitro constitutive ET-1 production by HMVEC-LBl. TGF-β increases ET-1 synthesis, and this may have clinical relevance in PAH. © 2008 Elsevier Inc. All rights reserved.

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Star, G. P., Giovinazzo, M., & Langleben, D. (2009). Effects of bone morphogenic proteins and transforming growth factor-beta on In-vitro production of endothelin-1 by human pulmonary microvascular endothelial cells. Vascular Pharmacology, 50(1–2), 45–50. https://doi.org/10.1016/j.vph.2008.09.001

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