| Autor: |
Justine Dhot, Marine Ferron, Valentine Prat, Antoine Persello, David Roul, David Stévant, Damien Guijarro, Nicolas Piriou, Virginie Aillerie, Angélique Erraud, Gilles Toumaniantz, Morteza Erfanian, Angela Tesse, Amandine Grabherr, Laurent Tesson, Séverine Menoret, Ignacio Anegon, Jean‐Noël Trochu, Marja Steenman, Michel De Waard, Bertrand Rozec, Benjamin Lauzier, Chantal Gauthier |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
ESC Heart Failure, Vol 7, Iss 6, Pp 4159-4171 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2055-5822 |
| DOI: |
10.1002/ehf2.13040 |
| Popis: |
Abstract Aims Diastolic dysfunction is common in cardiovascular diseases, particularly in the case of heart failure with preserved ejection fraction. The challenge is to develop adequate animal models to envision human therapies in the future. It has been hypothesized that this diastolic dysfunction is linked to alterations in the nitric oxide (•NO) pathway. To investigate this issue further, we investigated the cardiac functions of a transgenic rat model (Tgβ3) that overexpresses the human β3‐adrenoceptor (hβ3‐AR) in the endothelium with the underlying rationale that the •NO pathway should be stimulated in the endothelium. Methods and results Transgenic rats (Tgβ3) that express hβ3‐AR under the control of intercellular adhesion molecule 2 promoter were developed for a specific expression in endothelial cells. Transcriptomic analyses were performed on left ventricular tissue from 45‐week‐old rats. Among all altered genes, we focus on •NO synthase expression and endothelial function with arterial reactivity and evaluation of •NO and O2•− production. Cardiac function was characterized by echocardiography, invasive haemodynamic studies, and working heart studies. Transcriptome analyses illustrate that several key genes are regulated by the hβ3‐AR overexpression. Overexpression of hβ3‐AR leads to a reduction of Nos3 mRNA expression (−72%; P |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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