Transient gene therapy using cell cycle factors reverses renin–angiotensin–aldosterone system activation in heart failure rat model

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Salama A.B.M.; Abouleisa R.R.E.; Ou Q.; Tang X.-L.; Alhariry N.; Hassan S.; Gebreil A.; Dastagir M.; Abdulwali F.; Bolli R.; Mohamed T.M.A.

Journal: Molecular and Cellular Biochemistry

Publisher: Springer

Publication Date: 25 October 2022

Volume / Issue: Volume 478 / Issue 6

Pages: 1245–1250

ISSN: 3008177

DOI: 10.1007/s11010-022-04590-2

Scopus: View on Scopus

PubMed: 36282351

Document Type: Article

Access: All Open Access; Green Open Access

Authors and Affiliations

Salama A.B.M., Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States, Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt, Department of Cardiac Surgery, University of Verona, Verona, Italy, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Abouleisa R.R.E., Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Ou Q., Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Tang X.-L., Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Alhariry N., Department of Pathology, Faculty of Medicine, Suez University, Ismailia, Egypt, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Hassan S., Department of Electron Microscopy, Theodor Bilharz Research Institute, Imbaba Giza, Egypt, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Gebreil A., Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Dastagir M., Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Abdulwali F., Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Bolli R., Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States; Mohamed T.M.A., Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States, Department of Electron Microscopy, Theodor Bilharz Research Institute, Imbaba Giza, Egypt, Department of Bioengineering, University of Louisville, Louisville, KY, United States, Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, United States, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States, Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, 40202, KY, United States

Abstract

The loss of cardiomyocytes after myocardial infarction (MI) leads to heart failure. Recently, we demonstrated that transient overexpression of 4 cell cycle factors (4F), using a polycistronic non-integrating lentivirus (TNNT2-4F-NIL) resulted in significant improvement in cardiac function in a rat model of MI. Yet, it is crucial to demonstrate the reversal of the heart failure-related pathophysiological manifestations, such as renin–angiotensin–aldosterone system activation (RAAS). To assess that, Fisher 344 rats were randomized to receive TNNT2-4F-NIL or control virus seven days after coronary occlusion for 2 h followed by reperfusion. 4 months after treatment, N-terminal pro-brain natriuretic peptide, plasma renin activity, and aldosterone levels returned to the normal levels in rats treated with TNNT2-4F-NIL but not in vehicle-treated rats. Furthermore, the TNNT2-4F-NIL-treated group showed significantly less liver and kidney congestion than vehicle-treated rats. Thus, we conclude that in rat models of MI, TNNT2-4F-NIL reverses RAAS activation and subsequent systemic congestion. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

Basic science research; Gene therapy; Heart failure; Translational studies; Aldosterone; Animals; Cell Cycle; Kidney; Myocardial Infarction; Rats; Renin; Renin-Angiotensin System; amino terminal pro brain natriuretic peptide; angiotensin; cardiac troponin 2; cyclin B1; cyclin D1; cyclin dependent kinase 1; cyclin dependent kinase 4; lentivirus vector; troponin; troponin T; unclassified drug; animal experiment; animal model; animal tissue; Article; basic science; clinical assessment; controlled study; coronary occlusion; enzyme linked immunosorbent assay; gene overexpression; heart function; histopathology; kidney tissue; Lentivirus; liver tissue; male; myocardial ischemia reperfusion injury; non integrating lentivirus; nonhuman; plasma renin activity; promoter region; rat; rat model; renin angiotensin aldosterone system; therapy effect; transient gene therapy; treatment duration; treatment indication; animal; genetics; heart infarction; metabolism; randomized controlled trial

Citation Information

Scopus Citations: 4

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