Targeting systemic inflammation to save (micro-) vascular function - Game changer or vascular martyrdom?
- 1Cardioprotection Unite, Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, Essen, Germany
- 2Center for Cardiovascular Research and The Heart Center, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA
- 3Department of Pediatrics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
Abstract
The vasculature, particularly the lining endothelial cells, plays a key role in maintaining vascular homeostasis and enabling the functions of nearly all tissues by regulating blood flow, permeability, clotting, and immune cell trafficking.Consequently, endothelial dysfunction is a pivotal factor in the development and progression of major diseases, including (atherosclerotic) cardiovascular diseases and numerous inflammatory disorders.In patients with chronic, systemic inflammatory disorders, such as rheumatoid arthritis or inflammatory bowel disease, endothelial (micro-)vascular dysfunction has been identified as a potential key determinant for the increased risk for major adverse cardiovascular events (MACEs) (1).Therefore, the treatment of systemic inflammation is a promising key treatment target.In patients with inflammatory bowel disease, a massive increase in circulating proinflammatory cytokines trigger the activation of complex, receptor-mediated, intracellular signaling cascades, that involve among other the activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, resulting in the de novo synthesis of certain pro-inflammatory proteins responsible for cytokine production, or cellular proliferation or migration and thereby the further activation of inflammation (2).Therefore, medications that reduce the activity of pro-inflammatory cytokines (e.g., via binding of neutralizing antibodies to the cytokines, the inhibition of cytokine-specific receptors, and/or intra-cellular signaling cascades) were developed and approved for the treatment of autoimmune and inflammatory disorders (2).For example, tofacitinib is a non-selective inhibitor of JAK, primarily JAK1 and JAK3, whereas upadacitinib, a next-generation small molecule, is highly selective in its inhibition of JAK1.Both indirectly inhibit the receptormediated, intracellular signaling of a broad range of pro-inflammatory cytokines.
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BibTeX
@article{eickelmann2026targeting,
title = {{Targeting systemic inflammation to save (micro-) vascular function - Game changer or vascular martyrdom?}},
author = {Chantal Eickelmann and Aaron J. Trask},
journal = {American journal of physiology. Heart and circulatory physiology},
year = {2026},
month = sep,
doi = {10.1152/ajpheart.90034.2026},
url = {https://doi.org/10.1152/ajpheart.90034.2026},
note = {CC BY},
}
RIS
TY - JOUR
TI - Targeting systemic inflammation to save (micro-) vascular function - Game changer or vascular martyrdom?
AU - Chantal Eickelmann
AU - Aaron J. Trask
PY - 2026
DA - 2026/09/28
JO - American journal of physiology. Heart and circulatory physiology
DO - 10.1152/ajpheart.90034.2026
UR - https://doi.org/10.1152/ajpheart.90034.2026
AB - The vasculature, particularly the lining endothelial cells, plays a key role in maintaining vascular homeostasis and enabling the functions of nearly all tissues by regulating blood flow, permeability, clotting, and immune cell trafficking.Consequently, endothelial dysfunction is a pivotal factor in the development and progression of major diseases, including (atherosclerotic) cardiovascular diseases and numerous inflammatory disorders.In patients with chronic, systemic inflammatory disorders, such as rheumatoid arthritis or inflammatory bowel disease, endothelial (micro-)vascular dysfunction has been identified as a potential key determinant for the increased risk for major adverse cardiovascular events (MACEs) (1).Therefore, the treatment of systemic inflammation is a promising key treatment target.In patients with inflammatory bowel disease, a massive increase in circulating proinflammatory cytokines trigger the activation of complex, receptor-mediated, intracellular signaling cascades, that involve among other the activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, resulting in the de novo synthesis of certain pro-inflammatory proteins responsible for cytokine production, or cellular proliferation or migration and thereby the further activation of inflammation (2).Therefore, medications that reduce the activity of pro-inflammatory cytokines (e.g., via binding of neutralizing antibodies to the cytokines, the inhibition of cytokine-specific receptors, and/or intra-cellular signaling cascades) were developed and approved for the treatment of autoimmune and inflammatory disorders (2).For example, tofacitinib is a non-selective inhibitor of JAK, primarily JAK1 and JAK3, whereas upadacitinib, a next-generation small molecule, is highly selective in its inhibition of JAK1.Both indirectly inhibit the receptormediated, intracellular signaling of a broad range of pro-inflammatory cytokines.
SN - 0363-6135
SN - 1522-1539
ER -