| First Author | Meyer A | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 4 | Pages | 1064-74 |
| PubMed ID | 22134166 | Mgi Jnum | J:181748 |
| Mgi Id | MGI:5313800 | Doi | 10.1182/blood-2011-09-377648 |
| Citation | Meyer A, et al. (2012) Platelet TGF-beta1 contributions to plasma TGF-beta1, cardiac fibrosis, and systolic dysfunction in a mouse model of pressure overload. Blood 119(4):1064-74 |
| abstractText | Circulating platelets contain high concentrations of TGF-beta1 in their alpha-granules and release it on platelet adhesion/activation. We hypothesized that uncontrolled in vitro release of platelet TGF-beta1 may confound measurement of plasma TGF-beta1 in mice and that in vivo release and activation may contribute to cardiac pathology in response to constriction of the transverse aorta, which produces both high shear and cardiac pressure overload. Plasma TGF-beta1 levels in blood collected from C57Bl/6 mice by the standard retro-bulbar technique were much higher than those obtained when prostaglandin E was added to inhibit release or when blood was collected percutaneously from the left ventricle under ultrasound guidance. Even with optimal blood drawing, plasma TGF-beta1 was lower in mice rendered profoundly thrombocytopenic or mice with selectively low levels of platelet TGF-beta1 because of megakaryocyte-specific disruption of their TGF-beta1 gene (Tgfb1(flox)). Tgfb1(flox) mice were also partially protected from developing cardiac hypertrophy, fibrosis, and systolic dysfunction in response to transverse aortic constriction. These studies demonstrate that plasma TGF-beta1 levels can be assessed accurately, but it requires special precautions; that platelet TGF-beta1 contributes to plasma levels of TGF-beta1; and that platelet TGF-beta1 contributes to the pathologic cardiac changes that occur in response to aortic constriction. |
