JCI online early table of contents: April 1, 2008

TITLE: A novel antiplatelet antibody therapy that induces cAMP-dependent endocytosis of the GPVI/Fc receptor gamma-chain complex

AUTHOR CONTACT:
Hiroshi Takayama
The University of Shiga Prefecture, Shiga, Japan.
Phone: 81-749-28-8441; Fax: 81-749-28-8519; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=32513

CARDIOLOGY: Linking it all together: new pathway associated with pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is an increase in blood pressure in one or more of the blood vessels supplying the lungs. It can lead to shortness of breath, dizziness, fainting, and, in severe cases, heart failure. A marked proportion of cases are associated with loss-of-function or decreased expression in the lungs of the protein BMP-RII. New data, generated using mice and cultured human cells, by Marlene Rabinovitch and colleagues at Stanford University School of Medicine, have identified a signaling axis downstream of BMP-RII that might help explain the association between PAH and loss-of-function or decreased expression of the protein BMP-RII.

In the study, BMP-2–induced BMP-RII signaling was shown to inhibit the growth of human and mouse smooth muscle cells by inducing the protein PPAR-gamma to bind DNA, and both BMP-2 and a PPAR-gamma agonist were found to induce smooth muscle cells to secrete a protein known as apoE. Further analysis of human and mouse smooth muscle cells expressing reduced amounts of BMP-RII and smooth muscle cells from mice lacking either PPAR-gamma or apoE clearly indicated that the antiproliferative effect of BMP-2 was dependent on BMP-RII, PPAR-gamma, and apoE. As mice lacking PPAR-gamma in their smooth muscle cells were observed to develop PAH, the authors have suggested that PPAR-gamma agonists might benefit individuals with PAH.

TITLE: An antiproliferative BMP-2/PPAR-gamma/apoE axis in human and murine SMCs and its role in pulmonary hypertension

AUTHOR CONTACT:
Marlene Rabinovitch
Stanford University School of Medicine, Stanford, California, USA.
Phone: (650) 723-8239; Fax: (650) 723-6700; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=32503