Decorin-mediated transforming growth factor-beta inhibition ameliorates adverse cardiac remodeling
BACKGROUND: Implantation of a left ventricular assist device (LVAD) has been shown to induce regression of fibrosis in patients with congestive heart failure (CHF) and improve myocardial function. The mechanism of reverse remodeling after mechanical circulatory support (MCS), however, has not been fully characterized. In this study we examined the anti-fibrotic effects of decorin, an extracellular matrix (ECM) proteoglycan, on the transforming growth factor-beta (TGF-beta) pathway.
METHODS: Human myocardial tissue samples were obtained from patients undergoing LVAD implantation and again following subsequent transplantation after a sustained period of MCS. The specimens were examined by utilizing different molecular and histologic techniques, including human cardiac fibroblast in vitro studies. We assessed gene expression, mRNA and protein levels.
RESULTS: We found a significant decrease in interstitial fibrosis after MCS, with a decrease in collagen mRNA transcription rates, serving as an indirect measurement of collagen synthesis. Both the mRNA and protein levels of decorin were significantly increased after a period of MCS. Decorin mRNA was up-regulated by 44% after MCS (p < 0.01), which paralleled the increase in interstitial decorin deposition (p < 0.001). In addition, p-SMAD2, a molecular marker downstream of the TGF-beta pathway, was found to be inactivated after MCS (p < 0.02). Moreover, cultured human cardiac fibroblasts exposed to TGF-beta demonstrated decreased collagen production when exogenous decorin was added (p < 0.03).
CONCLUSIONS: The decorin molecule is potentially involved in reverse cardiac remodeling, by directly inhibiting the TGF-beta pathway and its pro-fibrotic effects on the failing human heart.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2007 |
|---|---|
| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
|---|---|
| Enthalten in: |
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation - 26(2007), 1 vom: 01. Jan., Seite 34-40 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jahanyar, Jama [VerfasserIn] |
|---|
| Themen: |
9007-34-5 |
|---|
| Anmerkungen: |
Date Completed 01.02.2007 Date Revised 18.11.2010 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM167799908 |
|---|
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| 100 | 1 | |a Jahanyar, Jama |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Decorin-mediated transforming growth factor-beta inhibition ameliorates adverse cardiac remodeling |
| 264 | 1 | |c 2007 | |
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| 500 | |a Date Completed 01.02.2007 | ||
| 500 | |a Date Revised 18.11.2010 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Implantation of a left ventricular assist device (LVAD) has been shown to induce regression of fibrosis in patients with congestive heart failure (CHF) and improve myocardial function. The mechanism of reverse remodeling after mechanical circulatory support (MCS), however, has not been fully characterized. In this study we examined the anti-fibrotic effects of decorin, an extracellular matrix (ECM) proteoglycan, on the transforming growth factor-beta (TGF-beta) pathway | ||
| 520 | |a METHODS: Human myocardial tissue samples were obtained from patients undergoing LVAD implantation and again following subsequent transplantation after a sustained period of MCS. The specimens were examined by utilizing different molecular and histologic techniques, including human cardiac fibroblast in vitro studies. We assessed gene expression, mRNA and protein levels | ||
| 520 | |a RESULTS: We found a significant decrease in interstitial fibrosis after MCS, with a decrease in collagen mRNA transcription rates, serving as an indirect measurement of collagen synthesis. Both the mRNA and protein levels of decorin were significantly increased after a period of MCS. Decorin mRNA was up-regulated by 44% after MCS (p < 0.01), which paralleled the increase in interstitial decorin deposition (p < 0.001). In addition, p-SMAD2, a molecular marker downstream of the TGF-beta pathway, was found to be inactivated after MCS (p < 0.02). Moreover, cultured human cardiac fibroblasts exposed to TGF-beta demonstrated decreased collagen production when exogenous decorin was added (p < 0.03) | ||
| 520 | |a CONCLUSIONS: The decorin molecule is potentially involved in reverse cardiac remodeling, by directly inhibiting the TGF-beta pathway and its pro-fibrotic effects on the failing human heart | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a DCN protein, human |2 NLM | |
| 650 | 7 | |a Decorin |2 NLM | |
| 650 | 7 | |a Extracellular Matrix Proteins |2 NLM | |
| 650 | 7 | |a Proteoglycans |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 650 | 7 | |a Collagen |2 NLM | |
| 650 | 7 | |a 9007-34-5 |2 NLM | |
| 700 | 1 | |a Joyce, David L |e verfasserin |4 aut | |
| 700 | 1 | |a Southard, Robert E |e verfasserin |4 aut | |
| 700 | 1 | |a Loebe, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Noon, George P |e verfasserin |4 aut | |
| 700 | 1 | |a Koerner, Michael M |e verfasserin |4 aut | |
| 700 | 1 | |a Torre-Amione, Guillermo |e verfasserin |4 aut | |
| 700 | 1 | |a Youker, Keith A |e verfasserin |4 aut | |
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