Article ; Online: Transient gene therapy using cell cycle factors reverses renin-angiotensin-aldosterone system activation in heart failure rat model.
Molecular and cellular biochemistry
2022 Volume 478, Issue 6, Page(s) 1245–1250
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 ... ...
| 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. |
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| MeSH term(s) | Animals ; Rats ; Aldosterone/metabolism ; Cell Cycle ; Heart Failure/genetics ; Heart Failure/therapy ; Heart Failure/metabolism ; Kidney/metabolism ; Myocardial Infarction/metabolism ; Renin/genetics ; Renin/metabolism ; Renin-Angiotensin System | |||||
| Chemical Substances | Aldosterone (4964P6T9RB) ; Renin (EC 3.4.23.15) | |||||
| Language | English | |||||
| Publishing date | 2022-10-25 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 184833-1 | |||||
| ISSN | 1573-4919 ; 0300-8177 | |||||
| ISSN (online) | 1573-4919 | |||||
| ISSN | 0300-8177 | |||||
| DOI | 10.1007/s11010-022-04590-2 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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