title: Platelet TGF-β1 contributions to plasma TGF-β1, cardiac fibrosis, and systolic dysfunction in a mouse model of pressure overload.
abstract: Circulating platelets contain high concentrations of TGF-β1 in their α-granules and release it on platelet adhesion/activation. We hypothesized that uncontrolled in vitro release of platelet TGF-β1 may confound measurement of plasma TGF-β1 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-β1 levels in blood collected from C57Bl/6 mice by the standard retro-bulbar technique were much higher than those obtained when prostaglandin E₁ 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-β1 was lower in mice rendered profoundly thrombocytopenic or mice with selectively low levels of platelet TGF-β1 because of megakaryocyte-specific disruption of their TGF-β1 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-β1 levels can be assessed accurately, but it requires special precautions; that platelet TGF-β1 contributes to plasma levels of TGF-β1; and that platelet TGF-β1 contributes to the pathologic cardiac changes that occur in response to aortic constriction.
authors: Laboratory of Blood and Vascular Biology, Rockefeller University, 1230 York Ave., New York, NY 10065, USA.
authors: Alexander
authors: A
authors: Meyer
authors: Wei
authors: W
authors: Wang
authors: Jiaxiang
authors: J
authors: Qu
authors: Lori
authors: L
authors: Croft
authors: Jay L
authors: JL
authors: Degen
authors: Barry S
authors: BS
authors: Coller
authors: Jasimuddin
authors: J
authors: Ahamed
mesh_terms: D000527:Alprostadil / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005355:Fibrosis / Q000209:etiology / Q000473:pathology; D006321:Heart / Q000503:physiopathology*; D006470:Hemorrhage / Q000209:etiology; D006973:Hypertension / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D019426:Integrases / Q000235:genetics; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000473:pathology*; D010974:Platelet Aggregation; D012868:Skin Abnormalities / Q000209:etiology; D013921:Thrombocytopenia / Q000209:etiology; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; C045073:Cre recombinase; D019426:Integrases; D000527:Alprostadil