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Immunological Control of Vascular Plasticity: Insights into Arteriogenesis, Angiogenesis, and Atherosclerosis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 June 2026 | Viewed by 2851

Special Issue Editors


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Guest Editor
1. Walter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität, 81377 Munich, Germany
2. Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universität München, Planegg-Martinsried, 82152 Munich, Germany
3. Institute of Surgical Research, Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, Germany
Interests: cardiovascular research; immunology
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Guest Editor
1. UNAM-UABJO Research Center, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca 68120, Mexico
2. Division of Postgraduate Studies and Research, Tijuana Institute of Technology, National Technological of Mexico (TecNM), Tijuana 22414, Mexico
Interests: basic science and clinical research in organ protection against acute ischaemia/reperfudion injury with a special focus on cardiac protection and acute inflammation and remodeling; basic science and translational research in atherosclerosis and chronic inflammation processes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Blood vessels possess an extraordinary capacity for adaptation, responding dynamically to physiological demands and pathological insults. Recent advances have revealed that this plasticity is not governed solely by hemodynamic forces or growth factor signaling, but is deeply intertwined with immune regulation. Innate and adaptive immune responses modulate vascular remodeling at every stage: from the initiation of arteriogenesis and the fine-tuning of angiogenic sprouting, to the progression and destabilization of atherosclerotic plaques.

This Special Issue will bring together ground-breaking research and distinguished perspectives at the intersection of vascular biology and immunology. We seek contributions that dissect the molecular and cellular mechanisms through which immune cells influence endothelial behavior, mural cell recruitment, extracellular matrix remodeling, and vascular integrity. Particularly welcome are studies integrating single-cell and spatial omics, advanced imaging, and in vivo modeling to illuminate immune–vascular interactions in both health and disease.

By bridging fundamental science with translational insight, this Special Issue aims to define a new framework for targeting immune pathways to modulate vascular growth, restore perfusion in ischemic tissues, or attenuate vascular inflammation. We invite original articles, expert reviews, and perspective pieces that will help shape the future of immunovascular medicine.

Prof. Dr. Elisabeth Deindl
Prof. Dr. Hector A. Cabrera-Fuentes
Guest Editors

Manuscript Submission Information

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Keywords

  • vascular plasticity
  • arteriogenesis
  • angiogenesis
  • atherosclerosis
  • immune modulation
  • inflammation and vascular remodeling
  • translational vascular immunology
  • smooth muscle cell-/endothelial cell proliferation
  • sterile inflammation
  • collateral artery growth

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Published Papers (2 papers)

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Research

20 pages, 3670 KB  
Article
Functional Coupling Between Voltage-Dependent Sodium Channels and Activation of the Ca2+ Signaling That Mediates Endothelial Cell Migration
by Hilda Espinoza and Xavier F. Figueroa
Int. J. Mol. Sci. 2026, 27(4), 1868; https://doi.org/10.3390/ijms27041868 - 15 Feb 2026
Viewed by 452
Abstract
Angiogenesis depends on Ca2+-mediated endothelial cell migration. The increase in intracellular Ca2+ concentration ([Ca2+]i) is coordinated by caveolae and the Cx43 hemichannel opening. However, the functional coupling of voltage-dependent Na+ channels (Nav) with [...] Read more.
Angiogenesis depends on Ca2+-mediated endothelial cell migration. The increase in intracellular Ca2+ concentration ([Ca2+]i) is coordinated by caveolae and the Cx43 hemichannel opening. However, the functional coupling of voltage-dependent Na+ channels (Nav) with Na+-Ca2+ exchanger reverse mode (NCXrm) activation may contribute to the response, which was evaluated using the wound-healing assay in primary cultures of rat mesenteric endothelial cells. Changes in [Ca2+]i, the hemichannel opening and the association of Nav channels with caveolin-1, a caveolae structural protein, were analyzed. Both endothelial cell migration and the associated Ca2+ signaling were inhibited by tetrodotoxin (TTX), a Nav channel blocker, lamotrigine, a preferential Nav1.2 inhibitor, or 4,9-anhydro-TTX, a specific Nav1.6 blocker. A similar result was found by disrupting caveolae organization with methyl-β-cyclodextrin or blocking NCXrm with SEA0400. TTX and SEA0400 also prevented Cx43 hemichannel opening, and tubular-like structure formation depended on Nav channels. An analysis using a proximity ligation assay showed that endothelial cell migration was paralleled by the progressive association of caveolin-1 with Nav1.2, but not Nav1.6, channels. These results suggest that the functional coupling of Nav1.2 and Nav1.6 channels with the activation of NCXrm and Cx43 hemichannels mediates the Ca2+ signaling associated with endothelial cell migration and angiogenesis, which provides new targets to modulate angiogenesis in physiological or pathological conditions. Full article
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19 pages, 6023 KB  
Article
Repurposing PDE5-Inhibitors: Sildenafil Drives Arteriogenesis via Localized Regenerative Inflammation
by Katharina Elbs, Lisa Bobrowski, Christoph Arnholdt, Matthias Kübler, Philipp Götz, Michael R. Rohrmoser, Daphne Merkus, Manuel Lasch and Elisabeth Deindl
Int. J. Mol. Sci. 2026, 27(2), 985; https://doi.org/10.3390/ijms27020985 - 19 Jan 2026
Cited by 1 | Viewed by 1970
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 [...] Read more.
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. Full article
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