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

Abou Bakr M Salama; Riham R E Abouleisa; Qinghui Ou; Xian-Liang Tang; Nashwah Alhariry; Sarah Hassan; Ahmad Gebreil; Muzammil Dastagir; Fareeha Abdulwali; Roberto Bolli; Tamer M A Mohamed

doi:10.1007/s11010-022-04590-2

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

Mol Cell Biochem. 2023 Jun;478(6):1245-1250. doi: 10.1007/s11010-022-04590-2. Epub 2022 Oct 25.

Authors

Abou Bakr M Salama^{1

2

3

4

5

6}, Riham R E Abouleisa^{1

4

5

6}, Qinghui Ou^{1

4

5

6}, Xian-Liang Tang^{1

4

5

6}, Nashwah Alhariry^{7

4

5

6}, Sarah Hassan^{8

4

5

6}, Ahmad Gebreil^{1

4

5

6}, Muzammil Dastagir^{1

4

5

6}, Fareeha Abdulwali^{1

4

5

6}, Roberto Bolli^{1

4

5

6}, Tamer M A Mohamed^{9

10

11

12

13

14

15}

Affiliations

¹ Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA.
² Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
³ Department of Cardiac Surgery, University of Verona, Verona, Italy.
⁴ Department of Bioengineering, University of Louisville, Louisville, KY, USA.
⁵ Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, USA.
⁶ Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA.
⁷ Department of Pathology, Faculty of Medicine, Suez University, Ismailia, Egypt.
⁸ Department of Electron Microscopy, Theodor Bilharz Research Institute, Imbaba Giza, Egypt.
⁹ Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA. tamer.mohamed@louisville.edu.
¹⁰ Department of Electron Microscopy, Theodor Bilharz Research Institute, Imbaba Giza, Egypt. tamer.mohamed@louisville.edu.
¹¹ Department of Bioengineering, University of Louisville, Louisville, KY, USA. tamer.mohamed@louisville.edu.
¹² Diabetes and Obesity Center, Department of Medicine, Envirome Institute, University of Louisville, Louisville, KY, USA. tamer.mohamed@louisville.edu.
¹³ Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA. tamer.mohamed@louisville.edu.
¹⁴ Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK. tamer.mohamed@louisville.edu.
¹⁵ Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY, 40202, USA. tamer.mohamed@louisville.edu.

PMID: 36282351
PMCID: PMC10126184 (available on 2024-06-01)
DOI: 10.1007/s11010-022-04590-2

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.

Keywords: Basic science research; Gene therapy; Heart failure; Translational studies.

MeSH terms

Aldosterone / metabolism
Animals
Cell Cycle
Heart Failure* / genetics
Heart Failure* / metabolism
Heart Failure* / therapy
Kidney / metabolism
Myocardial Infarction* / metabolism
Rats
Renin / genetics
Renin / metabolism
Renin-Angiotensin System

Substances

Aldosterone
Renin

Abstract

MeSH terms

Substances

Grants and funding