| Title: |
Repurposing PDE5-Inhibitors:Sildenafil Drives Arteriogenesis via Localized Regenerative Inflammation |
| Authors: |
Elbs, Katharina; Bobrowski, Lisa; Arnholdt, Christoph; Kübler, Matthias; Götz, Philipp; Rohrmoser, Michael R.; Merkus, Daphne; Lasch, Manuel; Deindl, Elisabeth |
| Source: |
Elbs, K, Bobrowski, L, Arnholdt, C, Kübler, M, Götz, P, Rohrmoser, M R, Merkus, D, Lasch, M & Deindl, E 2026, 'Repurposing PDE5-Inhibitors : Sildenafil Drives Arteriogenesis via Localized Regenerative Inflammation', International Journal of Molecular Sciences, vol. 27, no. 2, 985. https://doi.org/10.3390/ijms27020985 |
| Publication Year: |
2026 |
| Description: |
Arteriogenesis, the growth of pre-existing arterioles into functional collateral arteries, represents a key adaptive response to severe arterial stenosis. This process is driven by hemodynamic forces and a tightly coordinated inflammatory cascade. Here, we investigated the effects of pharmacological stimulation of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway using the phosphodiesterase-5 (PDE5) inhibitor Sildenafil on collateral vessel growth in a murine model of femoral artery ligation (FAL). Flow cytometric analyses revealed that Sildenafil treatment significantly enhanced platelet–leukocyte aggregate formation, a prerequisite for the subsequent initiation of a localized perivascular inflammation. Histological and immunofluorescence analyses further demonstrated a marked increase in mast cell recruitment and degranulation at early time points (days 1 and 3 post-FAL). In addition, Sildenafil promoted perivascular macrophage accumulation on days 3 and 7, with a pronounced shift toward an M2-like pro-regenerative polarization state, ultimately resulting in the enhanced proliferation of vascular cells and the enlargement of collateral diameters. Together, these findings identify Sildenafil as a potent enhancer of arteriogenesis through coordinated immune cell activation, stimulating vascular cell proliferation along with positive collateral outward remodeling. Thus, Sildenafil emerges as a promising therapeutic candidate to promote collateral artery growth in cardiovascular occlusive diseases. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1661-6596; 1422-0067 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41596630; info:eu-repo/semantics/altIdentifier/pissn/1661-6596; info:eu-repo/semantics/altIdentifier/eissn/1422-0067 |
| DOI: |
10.3390/ijms27020985 |
| Availability: |
https://pure.eur.nl/en/publications/1d5141de-b8e8-43fa-93d9-8823949a5158; https://doi.org/10.3390/ijms27020985; https://pure.eur.nl/ws/files/231333495/ijms-27-00985-v3.pdf; https://www.scopus.com/pages/publications/105028739462 |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.B04147DA |
| Database: |
BASE |