July 23, 2009

Treating Liver High Blood Pressure

Dr. Yasuni Nakanuma and colleagues of Kanazawa University Graduate School of Medicine in Kanazawa, Japan have discovered that BMP-7 (bone morphogenic protein-7) is a potential new therapy for treating high blood pressure in the liver. These results are presented in the August 2009 issue of The American Journal of Pathology.

Idiopathic portal hypertension (IPH) is a form of high blood pressure that often results from blockage of the peripheral veins in the liver. Cells that line blood vessels (endothelial cells) undergo endothelial-mesenchymal transition (EMT) to become more mobile; these cells may contribute to the fibrosis that causes IPH-associated blockage.

Kitao et al demonstrated that a molecule that contributes to the fibrotic process, TGF-ÃŽ²1 (transforming growth factor-ÃŽ²1), can induce EMT and that BMP-7, a member of the TGF-b superfamily, can preserve the endothelial phenotype. Indeed, patients with IPH have elevated levels of TGF-ÃŽ²1, but no difference in levels of BMP-7 compared with healthy controls. TGF-b and BMP-7 may therefore provide a potential target and agent, respectively, for treating IPH.

Kitao et al "suggest that EMT of the portal vein endothelium via TGF-ÃŽ²1/Smad activation is closely associated with the pathogenesis of portal venous stenosis of IPH "¦ [and that] BMP7 may act as an inhibitor of EndMT by antagonizing the effects of TGF-ÃŽ²1."

Kitao A, Sato Y, Kitamura S, Harada K, Sasaki M, Morikawa H, Shiomi S, Honda M, Matsui O, Nakanuma Y: Endothelial to mesenchymal transition via transforming growth factor-b1/Smad activation is associated with portal venous stenosis in idiopathic portal hypertension. Am J Pathol 2009, 175: 616-626


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American Journal of Pathology