Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms

Porcine heart xenotransplantation is a potential treatment for patients with end-stage heart failure. To understand molecular mechanisms of graft rejection after heart transplantation, we transplanted a 31-day-old alpha-1,3-galactosyltransferase knockout (GTKO) porcine heart to a five-year-old cynomolgus monkey. Histological and transcriptome analyses were conducted on xenografted cardiac tissue at rejection (nine days after transplantation). The recipient monkey’s blood parameters were analyzed on days −7, −3, 1, 4, and 7. Validation was conducted by quantitative real-time PCR (qPCR) with selected genes. A non-transplanted GTKO porcine heart from an age-matched litter was used as a control. The recipient monkey showed systemic inflammatory responses, and the rejected cardiac graft indicated myocardial infarction and cardiac fibrosis. The transplanted heart exhibited a total of 3748 differentially expressed genes compared to the non-transplanted heart transcriptome, with 2443 upregulated and 1305 downregulated genes. Key biological pathways involved at the terminal stage of graft rejection were cardiomyopathies, extracellular interactions, and ion channel activities. The results of qPCR evaluation were in agreement with the transcriptome data. Transcriptome analysis of porcine cardiac tissue at graft rejection reveals dysregulation of the key molecules and signaling pathways, which play relevant roles on structural and functional integrities of the heart.

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Fibrosis Protein-Protein Interactions from Google Matrix Analysis of MetaCore Network

International Journal of Molecular Sciences ◽

10.3390/ijms23010067 ◽

2021 ◽

Vol 23 (1) ◽

pp. 67

Author(s):

Ekaterina Kotelnikova ◽

Klaus M. Frahm ◽

Dima L. Shepelyansky ◽

Oksana Kunduzova

Keyword(s):

Heart Failure ◽

Protein Interactions ◽

Cardiac Fibrosis ◽

Matrix Analysis ◽

Great Promise ◽

Protein Protein Interactions ◽

Matrix Algorithms ◽

Google Matrix ◽

End Stage Heart Failure ◽

End Stage

Protein–protein interactions is a longstanding challenge in cardiac remodeling processes and heart failure. Here, we use the MetaCore network and the Google matrix algorithms for prediction of protein–protein interactions dictating cardiac fibrosis, a primary cause of end-stage heart failure. The developed algorithms allow identification of interactions between key proteins and predict new actors orchestrating fibroblast activation linked to fibrosis in mouse and human tissues. These data hold great promise for uncovering new therapeutic targets to limit myocardial fibrosis.

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Fibrosis protein-protein interactions from Google matrix analysis of MetaCore network

10.1101/2021.10.20.465138 ◽

2021 ◽

Author(s):

Ekaterina Kotelnikova ◽

Klaus M. Frahm ◽

Dima L. Shepelyansky ◽

Oksana Kunduzova

Keyword(s):

Heart Failure ◽

Protein Interactions ◽

Cardiac Fibrosis ◽

Matrix Analysis ◽

Great Promise ◽

Protein Protein Interactions ◽

Matrix Algorithms ◽

Google Matrix ◽

End Stage Heart Failure ◽

End Stage

Protein-protein interactions is a longstanding challenge in cardiac remodeling processes and heart failure. Here we use the MetaCore network and the Google matrix algorithms for prediction of protein-protein interactions dictating cardiac fibrosis, a primary causes of end-stage heart failure. The developed algorithms allow to identify interactions between key proteins and predict new actors orchestrating fibroblast activation linked to fibrosis in mouse and human tissues. These data hold great promise for uncovering new therapeutic targets to limit myocardial fibrosis.

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Ventricular Assist Devices: Current State and Challenges

Journal of Medical Devices ◽

10.1115/1.4037258 ◽

2017 ◽

Vol 11 (4) ◽

Cited By ~ 3

Author(s):

Siamak N. Doost ◽

Liang Zhong ◽

Yosry S. Morsi

Keyword(s):

Cardiac Tissue ◽

Heart Function ◽

Ventricular Assist Devices ◽

Assist Device ◽

Ventricular Assist ◽

Current State ◽

End Stage Heart Failure ◽

Mechanical Devices ◽

End Stage ◽

Promising Avenue

Cardiovascular disease (CVD), as the most prevalent human disease, incorporates a broad spectrum of cardiovascular system malfunctions/disorders. While cardiac transplantation is widely acknowledged as the optional treatment for patients suffering from end-stage heart failure (HF), due to its related drawbacks, such as the unavailability of heart donors, alternative treatments, i.e., implanting a ventricular assist device (VAD), it has been extensively utilized in recent years to recover heart function. However, this solution is thought problematic as it fails to satisfactorily provide lifelong support for patients at the end-stage of HF, nor does is solve the problem of their extensive postsurgery complications. In recent years, the huge technological advancements have enabled the manufacturing of a wide variety of reliable VAD devices, which provides a promising avenue for utilizing VAD implantation as the destination therapy (DT) in the future. Along with typical VAD systems, other innovative mechanical devices for cardiac support, as well as cell therapy and bioartificial cardiac tissue, have resulted in researchers proposing a new HF therapy. This paper aims to concisely review the current state of VAD technology, summarize recent advancements, discuss related complications, and argue for the development of the envisioned alternatives of HF therapy.

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Localization of endothelial nitric oxide synthase in the normal and failing human atrial myocardium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100166397 ◽

1996 ◽

Vol 54 ◽

pp. 786-787

Author(s):

Chi-Ming Wei ◽

Margarita Bracamonte ◽

Shi-Wen Jiang ◽

Richard C. Daly ◽

Christopher G.A. McGregor ◽

...

Keyword(s):

Nitric Oxide ◽

Heart Failure ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Cardiac Tissues ◽

Mammalian Tissues ◽

End Stage Heart Failure ◽

End Stage ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Nitric oxide (NO) is a potent endothelium-derived relaxing factor which also may modulate cardiomyocyte inotropism and growth via increasing cGMP. While endothelial nitric oxide synthase (eNOS) isoforms have been detected in non-human mammalian tissues, expression and localization of eNOS in the normal and failing human myocardium are poorly defined. Therefore, the present study was designed to investigate eNOS in human cardiac tissues in the presence and absence of congestive heart failure (CHF).Normal and failing atrial tissue were obtained from six cardiac donors and six end-stage heart failure patients undergoing primary cardiac transplantation. ENOS protein expression and localization was investigated utilizing Western blot analysis and immunohistochemical staining with the polyclonal rabbit antibody to eNOS (Transduction Laboratories, Lexington, Kentucky).

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