Repurposing PDE5-Inhibitors: Sildenafil Drives Arteriogenesis via Localized Regenerative Inflammation
Elbs K, Bobrowski L, Arnholdt C, Kübler M, Götz P, Rohrmoser MR, Merkus D, Lasch M, Deindl E (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 27
Article Number: 985
Journal Issue: 2
DOI: 10.3390/ijms27020985
Abstract
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.
Involved external institutions
Germany (DE)How to cite
APA:
Elbs, K., Bobrowski, L., Arnholdt, C., Kübler, M., Götz, P., Rohrmoser, M.R.,... Deindl, E. (2026). Repurposing PDE5-Inhibitors: Sildenafil Drives Arteriogenesis via Localized Regenerative Inflammation. International Journal of Molecular Sciences, 27(2). https://doi.org/10.3390/ijms27020985
MLA:
Elbs, Katharina, et al. "Repurposing PDE5-Inhibitors: Sildenafil Drives Arteriogenesis via Localized Regenerative Inflammation." International Journal of Molecular Sciences 27.2 (2026).
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