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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.healun.2006.10.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Studies of methylated CpG ODN from subsp. in a murine model: Implications for treatment of human allergic disease.
Allergy Asthma Proc
January 2025
From the Department of Microbiology-Immunology, Georgetown University Medical Center, Washington, D.C.
Allergen immunotherapy (AIT) is currently the most effective immunologic form of treatment for patients with atopic allergic diseases commonly used by allergist/immunologists to reduce allergic symptoms by gradually desensitizing the immune system to specific allergens. Currently, the primary mechanism of AIT emphasizes the crucial role of immune regulation, which involves a shift from a T-helper type 2 (Th2) cell response, which promotes allergy, to a T-regulatory (Treg) cell population, which inhibits the allergic inflammatory response through the production of immunosuppressive cytokines interleukin 10 and transforming growth factor β, which play pivotal roles in suppressing the allergic reaction. In a series of previous in vitro and in vivo experiments, we have demonstrated the capacity of synthetic methylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) moieties as well as methylated genomic DNA ODN motifs from Bifidobacterium longum subspecies infantis to activate Treg cell differentiation in contrast to the unmethylated ODN moiety, which promotes proinflammatory responses driven by Th17-mediated responses.
View Article and Find Full Text PDF3-Bromo-4,5-dihydroxybenzaldehyde Attenuates Allergic Contact Dermatitis by Generating CD4Foxp3 T cells.
In Vivo
December 2024
Department of Medicine, College of Medicine, Jeju National University, Jeju, Republic of Korea;
Background/aim: Regulatory T cells (Tregs) play a crucial role in inflammatory responses by regulating the activity of various immune cells. M2 macrophages induced by IL-10 and TGF-β exhibit anti-inflammatory functions and induce Treg differentiation. Although the beneficial effects of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) on various diseases have been widely reported, the mechanisms, through which it alleviates allergic contact dermatitis (ACD) via Tregs and macrophages, are not well understood.
View Article and Find Full Text PDFIdentification of a Potent CDK8 Inhibitor Using Structure-Based Virtual Screening.
J Chem Inf Model
December 2024
School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Pulmonary fibrosis is excessive scarring of the lung tissues. Transforming growth factor-beta (TGF-β) has been implicated in pulmonary fibrosis due to its ability to induce the epithelial-to-mesenchymal transition (EMT) and promote epithelial cell migration. Cyclin-dependent kinase 8 (CDK8) can mediate the TGF-β signaling pathways and could function as an alternative therapeutic target for treating pulmonary fibrosis.
View Article and Find Full Text PDFUse of platelet-rich plasma in rheumatic diseases.
Rheumatol Int
December 2024
Department of Surgery and Anesthesiology-Intensive Care, Khoja Akhmet Yassawi International Kazakh-Turkish University, Shymkent, Kazakhstan.
Platelet-rich plasma (PRP) has gained increasing recognition as a promising therapeutic agent in managing rheumatic diseases. Conventional treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs), primarily act on reducing inflammation but fail to address the underlying mechanisms of connective tissue degradation. PRP, an autologous preparation enriched with growth factors and bioactive molecules, is pivotal in modulating inflammation and fostering tissue regeneration.
View Article and Find Full Text PDFSmall spheroids for head and neck cartilage tissue engineering.
Sci Rep
December 2024
Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
The demand for cartilage reconstruction in the head and neck region arises frequently due to trauma, malignancies, and hereditary diseases. Traditional tissue engineering produces cartilage from a small biopsy by combining biomaterials and expanded cells. However, this top-down approach is associated with several limitations, including the non-uniform distribution of cells, lack of physiological cell-cell and cell-matrix interactions, and compromised mechanical properties and tissue architecture.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!