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Blockage of the adenosine A2B receptor prevents cardiac fibroblasts overgrowth in rats with pulmonary arterial hypertension.
- Source :
- Purinergic Signalling; Apr2024, Vol. 20 Issue 2, p163-179, 17p
- Publication Year :
- 2024
-
Abstract
- Sustained pressure overload and fibrosis of the right ventricle (RV) are the leading causes of mortality in pulmonary arterial hypertension (PAH). Although the role of adenosine in PAH has been attributed to the control of pulmonary vascular tone, cardiac reserve, and inflammatory processes, the involvement of the nucleoside in RV remodelling remains poorly understood. Conflicting results exist on targeting the low-affinity adenosine A<subscript>2B</subscript> receptor (A<subscript>2B</subscript>AR) for the treatment of PAH mostly because it displays dual roles in acute vs. chronic lung diseases. Herein, we investigated the role of the A<subscript>2B</subscript>AR in the viability/proliferation and collagen production by cardiac fibroblasts (CFs) isolated from RVs of rats with monocrotaline (MCT)-induced PAH. CFs from MCT-treated rats display higher cell viability/proliferation capacity and overexpress A<subscript>2B</subscript>AR compared to the cells from healthy littermates. The enzymatically stable adenosine analogue, 5′-N-ethylcarboxamidoadenosine (NECA, 1–30 μM), concentration-dependently increased growth, and type I collagen production by CFs originated from control and PAH rats, but its effects were more prominent in cells from rats with PAH. Blockage of the A<subscript>2B</subscript>AR with PSB603 (100 nM), but not of the A<subscript>2A</subscript>AR with SCH442416 (100 nM), attenuated the proliferative effect of NECA in CFs from PAH rats. The A<subscript>2A</subscript>AR agonist, CGS21680 (3 and 10 nM), was virtually devoid of effect. Overall, data suggest that adenosine signalling via A<subscript>2B</subscript>AR may contribute to RV overgrowth secondary to PAH. Therefore, blockage of the A<subscript>2A</subscript>AR may be a valuable therapeutic alternative to mitigate cardiac remodelling and prevent right heart failure in PAH patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15739538
- Volume :
- 20
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Purinergic Signalling
- Publication Type :
- Academic Journal
- Accession number :
- 176466444
- Full Text :
- https://doi.org/10.1007/s11302-023-09952-z