Decorin-mediated transforming growth factor-beta inhibition ameliorates adverse cardiac remodeling. J Heart Lung Transplant 2007 Jan;26(1):34-40
Date
01/20/2007Pubmed ID
17234515DOI
10.1016/j.healun.2006.10.005Scopus ID
2-s2.0-33846233906 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
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.
Author List
Jahanyar J, Joyce DL, Southard RE, Loebe M, Noon GP, Koerner MM, Torre-Amione G, Youker KAMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Cells, Cultured
Collagen
Decorin
Endomyocardial Fibrosis
Extracellular Matrix Proteins
Female
Fibroblasts
Gene Expression Regulation
Heart Failure
Heart Ventricles
Heart-Assist Devices
Humans
Male
Microscopy, Fluorescence
Middle Aged
Polymerase Chain Reaction
Proteoglycans
RNA, Messenger
Transforming Growth Factor beta
Treatment Outcome
Ventricular Remodeling
