Abstract 335: Deletion Of Bmper In Mice Identifies A Novel Bmp-dependent Pathway For Regulating Cardiomyocyte Hypertrophy
| Autor: | Rongqin Ren, Monte Willis, Holly McDonough, Rusty Kelley, Yaxu Wu, Cam Patterson |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Circulation. 116 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Bone morphogenetic proteins (BMP) are members of the TGF-β superfamily that regulate numerous cellular functions during development and in adulthood. We recently reported that Bmper (BMP-binding endothelial precursor-derived regulator) is an extracellular protein that modulates BMP activities. We created knock-in mice in which GFP replaces exons 1 and 2 of the Bmper gene, and found that ventricular cardiomyocytes abundantly expressed Bmper in vivo, especially during late stages of cardiac development in utero. To explore the role of Bmper in cardiomyocyte differentiation, in vitro hypertrophy assays were performed using embryonic day 18.5 cardiomyocytes from Bmper −/− and Bmper +/+ mice and cells were treated with vehicle, BMP2 (100 ng/ml), or the alpha-adrenergic agonist phenylephrine (100 μM) for 48 hours. Phenylephrine treatment induced a ~30% cell size increase in wild-type cardiomyocytes, whereas to our surprise BMP2 elicited an ~80% increase in size, indicating a potent hypertrophic effect of BMP2 on cardiomyocytes. In comparison to wild-type cardiomyocytes, Bmper −/− cells were ~100% larger without any treatment and were not further responsive to BMP2 or phenylephrine. Real-time PCR analysis of BMP2- and phenylephrine-treated wild-type cardiomyocytes revealed up-regulation of cardiac differentiation markers (including atrial natriuretic factor, smooth muscle actin, alpha-myosin heavy chain, and GATA2) and BMP signaling components (including BMP ligands, receptors, and Smad1/5/8). These same markers were upregulated in Bmper −/− cardiomyocytes, even in the absence of treatment. These observations indicate that the BMP pathway has a previously undisclosed role in regulating hypertrophy in cardiomyocytes and that Bmper, as a BMP antagonist, dramatically attenuates BMP-induced cardiomyocyte hypertrophy. |
| Databáze: | OpenAIRE |
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