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Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably....
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| Zeitschriftentitel: | Circulation |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | Circulation, 132, 2015, suppl_3 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Ovid Technologies (Wolters Kluwer Health)
|
| Schlagwörter: |
| author_facet |
Nistal, Francisco Merino, David Villar, Ana V Garcia-Lopez, Raquel Tramullas, Mónica Ruiz-Guerrero, Luis Ribas, Catalina Hurle, Maria A Nistal, Francisco Merino, David Villar, Ana V Garcia-Lopez, Raquel Tramullas, Mónica Ruiz-Guerrero, Luis Ribas, Catalina Hurle, Maria A |
|---|---|
| author |
Nistal, Francisco Merino, David Villar, Ana V Garcia-Lopez, Raquel Tramullas, Mónica Ruiz-Guerrero, Luis Ribas, Catalina Hurle, Maria A |
| spellingShingle |
Nistal, Francisco Merino, David Villar, Ana V Garcia-Lopez, Raquel Tramullas, Mónica Ruiz-Guerrero, Luis Ribas, Catalina Hurle, Maria A Circulation Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study Physiology (medical) Cardiology and Cardiovascular Medicine |
| author_sort |
nistal, francisco |
| spelling |
Nistal, Francisco Merino, David Villar, Ana V Garcia-Lopez, Raquel Tramullas, Mónica Ruiz-Guerrero, Luis Ribas, Catalina Hurle, Maria A 0009-7322 1524-4539 Ovid Technologies (Wolters Kluwer Health) Physiology (medical) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/circ.132.suppl_3.14298 <jats:p> <jats:bold>Introduction:</jats:bold> Cytokynes of the Transforming Growth Factor-β(TGF-β) superfamily are involved in tissue fibrosis: TGF-β promotes fibrosis, whereas Bone Morphogenetic Protein-7 (BMP-7) is antifibrotic. Hypothesis: (i) LV remodeling in the pressure overload condition associates disequilibrium in the cellular signals mediated by these cytokynes; and (ii) BMP-7 exerts beneficial effects on LV remodeling and on reverse remodeling. </jats:p> <jats:p> <jats:bold>Methods:</jats:bold> We studied patients with aortic stenosis (AS; n=45) and surgical controls (n=30), and mice subjected to transverse aortic constriction (TAC; n=24). LV morphology and function were assessed by echocardiography; LV samples were analyzed by qPCR, immunoblotting and histology. </jats:p> <jats:p> <jats:bold>Results:</jats:bold> Pressure overload diminished the expression of BMP-7 and its effectors pSmad1/5/8 and increased the ratio TGF-β/BMP-7 in the LV from AS-patients and TAC-mice. BMP-7 expression correlated inversely with collagens, fibronectin and β-myosin heavy chain, with the degree of hypertrophy, and with the severity of diastolic dysfunction, and directly with systolic function. Multiple linear regression analysis disclosed BMP-7 and TGF-β as predictors, negative and positive, respectively, of hypertrophy. BMP-7 prevented the hypertrophic program elicited by TGF-β in cultured cardiomyocytes, and the transcriptional activation of Col1A1 promoter-luciferase reporter in NIH-3T3 fibroblasts. In TAC-mice, BMP-7 gain-of-function attenuated the development of structural damage and dysfunction, halted ongoing remodeling and facilitated reverse remodeling. BMP-7 loss-of-function exerted opposite effects. Luciferase reporter assays in NIH-3T3 fibroblasts suggested that BMP-7 promoted the transcription of the inhibitory Smad7, who in turn has a repressing effect on TGFβ signaling. Accordingly, in AS-patients and TAC-mice, the LV expressions of Smad7 and BMP-7 correlated directly. </jats:p> <jats:p> <jats:bold>Conclusion:</jats:bold> The disequilibrium between BMP-7 and TGF-β signals plays a relevant role in the pressure overload-induced myocardial remodeling in TAC-mice and AS-patients. We suggest that BMP-7 antagonizes the hypertrophic and profibrogenic effects of TGF-β through a mechanism involving Smad7. Funding: PI12/00999; RD12/0042/0018; RD12/0042/0012. </jats:p> Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study Circulation |
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10.1161/circ.132.suppl_3.14298 |
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Biologie Medizin |
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Ovid Technologies (Wolters Kluwer Health), 2015 |
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0009-7322 1524-4539 |
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Circulation |
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| title |
Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_unstemmed |
Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_full |
Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_fullStr |
Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_full_unstemmed |
Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_short |
Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_sort |
abstract 14298: the normal balance between antifibrotic bmp-7 and profibrotic tgf-β signaling is lost on the pressure overload-induced lv remodeling and can be modified favorably. a translational study |
| topic |
Physiology (medical) Cardiology and Cardiovascular Medicine |
| url |
http://dx.doi.org/10.1161/circ.132.suppl_3.14298 |
| publishDate |
2015 |
| physical |
|
| description |
<jats:p>
<jats:bold>Introduction:</jats:bold>
Cytokynes of the Transforming Growth Factor-β(TGF-β) superfamily are involved in tissue fibrosis: TGF-β promotes fibrosis, whereas Bone Morphogenetic Protein-7 (BMP-7) is antifibrotic. Hypothesis: (i) LV remodeling in the pressure overload condition associates disequilibrium in the cellular signals mediated by these cytokynes; and (ii) BMP-7 exerts beneficial effects on LV remodeling and on reverse remodeling.
</jats:p>
<jats:p>
<jats:bold>Methods:</jats:bold>
We studied patients with aortic stenosis (AS; n=45) and surgical controls (n=30), and mice subjected to transverse aortic constriction (TAC; n=24). LV morphology and function were assessed by echocardiography; LV samples were analyzed by qPCR, immunoblotting and histology.
</jats:p>
<jats:p>
<jats:bold>Results:</jats:bold>
Pressure overload diminished the expression of BMP-7 and its effectors pSmad1/5/8 and increased the ratio TGF-β/BMP-7 in the LV from AS-patients and TAC-mice. BMP-7 expression correlated inversely with collagens, fibronectin and β-myosin heavy chain, with the degree of hypertrophy, and with the severity of diastolic dysfunction, and directly with systolic function. Multiple linear regression analysis disclosed BMP-7 and TGF-β as predictors, negative and positive, respectively, of hypertrophy. BMP-7 prevented the hypertrophic program elicited by TGF-β in cultured cardiomyocytes, and the transcriptional activation of Col1A1 promoter-luciferase reporter in NIH-3T3 fibroblasts. In TAC-mice, BMP-7 gain-of-function attenuated the development of structural damage and dysfunction, halted ongoing remodeling and facilitated reverse remodeling. BMP-7 loss-of-function exerted opposite effects. Luciferase reporter assays in NIH-3T3 fibroblasts suggested that BMP-7 promoted the transcription of the inhibitory Smad7, who in turn has a repressing effect on TGFβ signaling. Accordingly, in AS-patients and TAC-mice, the LV expressions of Smad7 and BMP-7 correlated directly.
</jats:p>
<jats:p>
<jats:bold>Conclusion:</jats:bold>
The disequilibrium between BMP-7 and TGF-β signals plays a relevant role in the pressure overload-induced myocardial remodeling in TAC-mice and AS-patients. We suggest that BMP-7 antagonizes the hypertrophic and profibrogenic effects of TGF-β through a mechanism involving Smad7. Funding: PI12/00999; RD12/0042/0018; RD12/0042/0012.
</jats:p> |
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| author | Nistal, Francisco, Merino, David, Villar, Ana V, Garcia-Lopez, Raquel, Tramullas, Mónica, Ruiz-Guerrero, Luis, Ribas, Catalina, Hurle, Maria A |
| author_facet | Nistal, Francisco, Merino, David, Villar, Ana V, Garcia-Lopez, Raquel, Tramullas, Mónica, Ruiz-Guerrero, Luis, Ribas, Catalina, Hurle, Maria A, Nistal, Francisco, Merino, David, Villar, Ana V, Garcia-Lopez, Raquel, Tramullas, Mónica, Ruiz-Guerrero, Luis, Ribas, Catalina, Hurle, Maria A |
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| description | <jats:p> <jats:bold>Introduction:</jats:bold> Cytokynes of the Transforming Growth Factor-β(TGF-β) superfamily are involved in tissue fibrosis: TGF-β promotes fibrosis, whereas Bone Morphogenetic Protein-7 (BMP-7) is antifibrotic. Hypothesis: (i) LV remodeling in the pressure overload condition associates disequilibrium in the cellular signals mediated by these cytokynes; and (ii) BMP-7 exerts beneficial effects on LV remodeling and on reverse remodeling. </jats:p> <jats:p> <jats:bold>Methods:</jats:bold> We studied patients with aortic stenosis (AS; n=45) and surgical controls (n=30), and mice subjected to transverse aortic constriction (TAC; n=24). LV morphology and function were assessed by echocardiography; LV samples were analyzed by qPCR, immunoblotting and histology. </jats:p> <jats:p> <jats:bold>Results:</jats:bold> Pressure overload diminished the expression of BMP-7 and its effectors pSmad1/5/8 and increased the ratio TGF-β/BMP-7 in the LV from AS-patients and TAC-mice. BMP-7 expression correlated inversely with collagens, fibronectin and β-myosin heavy chain, with the degree of hypertrophy, and with the severity of diastolic dysfunction, and directly with systolic function. Multiple linear regression analysis disclosed BMP-7 and TGF-β as predictors, negative and positive, respectively, of hypertrophy. BMP-7 prevented the hypertrophic program elicited by TGF-β in cultured cardiomyocytes, and the transcriptional activation of Col1A1 promoter-luciferase reporter in NIH-3T3 fibroblasts. In TAC-mice, BMP-7 gain-of-function attenuated the development of structural damage and dysfunction, halted ongoing remodeling and facilitated reverse remodeling. BMP-7 loss-of-function exerted opposite effects. Luciferase reporter assays in NIH-3T3 fibroblasts suggested that BMP-7 promoted the transcription of the inhibitory Smad7, who in turn has a repressing effect on TGFβ signaling. Accordingly, in AS-patients and TAC-mice, the LV expressions of Smad7 and BMP-7 correlated directly. </jats:p> <jats:p> <jats:bold>Conclusion:</jats:bold> The disequilibrium between BMP-7 and TGF-β signals plays a relevant role in the pressure overload-induced myocardial remodeling in TAC-mice and AS-patients. We suggest that BMP-7 antagonizes the hypertrophic and profibrogenic effects of TGF-β through a mechanism involving Smad7. Funding: PI12/00999; RD12/0042/0018; RD12/0042/0012. </jats:p> |
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| spelling | Nistal, Francisco Merino, David Villar, Ana V Garcia-Lopez, Raquel Tramullas, Mónica Ruiz-Guerrero, Luis Ribas, Catalina Hurle, Maria A 0009-7322 1524-4539 Ovid Technologies (Wolters Kluwer Health) Physiology (medical) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/circ.132.suppl_3.14298 <jats:p> <jats:bold>Introduction:</jats:bold> Cytokynes of the Transforming Growth Factor-β(TGF-β) superfamily are involved in tissue fibrosis: TGF-β promotes fibrosis, whereas Bone Morphogenetic Protein-7 (BMP-7) is antifibrotic. Hypothesis: (i) LV remodeling in the pressure overload condition associates disequilibrium in the cellular signals mediated by these cytokynes; and (ii) BMP-7 exerts beneficial effects on LV remodeling and on reverse remodeling. </jats:p> <jats:p> <jats:bold>Methods:</jats:bold> We studied patients with aortic stenosis (AS; n=45) and surgical controls (n=30), and mice subjected to transverse aortic constriction (TAC; n=24). LV morphology and function were assessed by echocardiography; LV samples were analyzed by qPCR, immunoblotting and histology. </jats:p> <jats:p> <jats:bold>Results:</jats:bold> Pressure overload diminished the expression of BMP-7 and its effectors pSmad1/5/8 and increased the ratio TGF-β/BMP-7 in the LV from AS-patients and TAC-mice. BMP-7 expression correlated inversely with collagens, fibronectin and β-myosin heavy chain, with the degree of hypertrophy, and with the severity of diastolic dysfunction, and directly with systolic function. Multiple linear regression analysis disclosed BMP-7 and TGF-β as predictors, negative and positive, respectively, of hypertrophy. BMP-7 prevented the hypertrophic program elicited by TGF-β in cultured cardiomyocytes, and the transcriptional activation of Col1A1 promoter-luciferase reporter in NIH-3T3 fibroblasts. In TAC-mice, BMP-7 gain-of-function attenuated the development of structural damage and dysfunction, halted ongoing remodeling and facilitated reverse remodeling. BMP-7 loss-of-function exerted opposite effects. Luciferase reporter assays in NIH-3T3 fibroblasts suggested that BMP-7 promoted the transcription of the inhibitory Smad7, who in turn has a repressing effect on TGFβ signaling. Accordingly, in AS-patients and TAC-mice, the LV expressions of Smad7 and BMP-7 correlated directly. </jats:p> <jats:p> <jats:bold>Conclusion:</jats:bold> The disequilibrium between BMP-7 and TGF-β signals plays a relevant role in the pressure overload-induced myocardial remodeling in TAC-mice and AS-patients. We suggest that BMP-7 antagonizes the hypertrophic and profibrogenic effects of TGF-β through a mechanism involving Smad7. Funding: PI12/00999; RD12/0042/0018; RD12/0042/0012. </jats:p> Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study Circulation |
| spellingShingle | Nistal, Francisco, Merino, David, Villar, Ana V, Garcia-Lopez, Raquel, Tramullas, Mónica, Ruiz-Guerrero, Luis, Ribas, Catalina, Hurle, Maria A, Circulation, Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study, Physiology (medical), Cardiology and Cardiovascular Medicine |
| title | Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_full | Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_fullStr | Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_full_unstemmed | Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_short | Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| title_sort | abstract 14298: the normal balance between antifibrotic bmp-7 and profibrotic tgf-β signaling is lost on the pressure overload-induced lv remodeling and can be modified favorably. a translational study |
| title_unstemmed | Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study |
| topic | Physiology (medical), Cardiology and Cardiovascular Medicine |
| url | http://dx.doi.org/10.1161/circ.132.suppl_3.14298 |