Skeletal muscle vasomotor function, ergonomics, histopathology, and gene expression in Veterans with Gulf War Illness
Abstract
Background: Gulf War Illness (GWI) is a constellation of debilitating symptoms including fatigue and muscle weakness reported in one-third of Veterans from coalition countries deployed in the Gulf War (1990-1991). We hypothesized that muscle vasomotor function, physiology, structure, and gene expression were different between 49 cases with GWI and 22 controls Veterans defined by the symptom-based Kansas GWI questionnaire.
Methods: We assessed profunda artery microvascular vasomotion with intra-arterial infusions of acetylcholine 10 ⁻⁴ M (endothelium-dependent) and adenosine (endothelium-independent), and aerobic function by a symptom-limited cardiopulmonary exercise test. Biopsies of the vastus lateralis were frozen for later histology, western blot analysis, and unbiased gene expression using bulk RNA sequencing (RNAseq).
Results: Veteran GWI cases and controls have similar microvascular endothelium-dependent function (difference = −6.6%, 95%CI = −31.5%, 18.4%), endothelium independent function (difference = −10%, 95%CI = −95%, 75%) vasomotor function. The study has adequate power to identify known factors related to impaired microvascular endothelium-dependent function, such as smoking (difference = −42.5%, 95%CI = −79.0%, − 6.0%). Cases and controls have similar aerobic capacity (difference peak V̇O ₂ = −1.5, 95%CI = −4.8, 1.9 mL/kg/min), V̇O ₂ at anabolic threshold (difference = −1.0, 95%CI = −4.1, 2.1 mL/kg/min). Cases and controls have similar muscle histology, mitochondrial volume and density, and content of glycolytic, anerobic, tricarboxylic acid cycle and mitochondrial oxidative phosphorylation enzymes. RNAseq reveals no metabolic pathway gene dysregulation associated with GWI.
Conclusions: Symptoms of GWI triggered by the physical and psychological trauma of war are unrelated to multiple peripheral vascular and muscle parameters. GWI patients should obtain a similar training effect from physical activity as those without GWI.
Related
- Cytokine expression and secretion by skeletal muscle cells: regulatory mechanisms and exercise effects
- Maternal hyperglycemia impairs postnatal skeletal muscle growth and induces stage-dependent gene expression changes in mouse offspring
- Does the aging skeletal muscle maintain its endocrine function?
- GLP-1-Based Pharmacotherapies and Skeletal Muscle Health in Obesity: A Narrative Review of Body Composition, Muscle Function, and Sarcopenia-Related Outcomes
- Magnetomyography for skeletal muscle function assessment: prospective applications in sarcopenia
BibTeX
@article{kinlay2026skeletal,
title = {{Skeletal muscle vasomotor function, ergonomics, histopathology, and gene expression in Veterans with Gulf War Illness}},
author = {Scott Kinlay and Sara Temiyasathit and Samantha Ly and Margot Quinn and Mariah Bundy and Melissa Chin and Jacquelyn-My Do and Shannon Johnson and Kelly Allsup and Micah L. Burch and Manu Beerens and Daniel E. Forman and Maxine Krengel and Calum A. MacRae},
journal = {Communications Medicine},
year = {2026},
month = oct,
doi = {10.1038/s43856-026-01927-6},
url = {https://www.nature.com/articles/s43856-026-01927-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Skeletal muscle vasomotor function, ergonomics, histopathology, and gene expression in Veterans with Gulf War Illness
AU - Scott Kinlay
AU - Sara Temiyasathit
AU - Samantha Ly
AU - Margot Quinn
AU - Mariah Bundy
AU - Melissa Chin
AU - Jacquelyn-My Do
AU - Shannon Johnson
AU - Kelly Allsup
AU - Micah L. Burch
AU - Manu Beerens
AU - Daniel E. Forman
AU - Maxine Krengel
AU - Calum A. MacRae
PY - 2026
DA - 2026/10/06
JO - Communications Medicine
DO - 10.1038/s43856-026-01927-6
UR - https://www.nature.com/articles/s43856-026-01927-6
AB - Background: Gulf War Illness (GWI) is a constellation of debilitating symptoms including fatigue and muscle weakness reported in one-third of Veterans from coalition countries deployed in the Gulf War (1990-1991). We hypothesized that muscle vasomotor function, physiology, structure, and gene expression were different between 49 cases with GWI and 22 controls Veterans defined by the symptom-based Kansas GWI questionnaire. Methods: We assessed profunda artery microvascular vasomotion with intra-arterial infusions of acetylcholine 10 ⁻⁴ M (endothelium-dependent) and adenosine (endothelium-independent), and aerobic function by a symptom-limited cardiopulmonary exercise test. Biopsies of the vastus lateralis were frozen for later histology, western blot analysis, and unbiased gene expression using bulk RNA sequencing (RNAseq). Results: Veteran GWI cases and controls have similar microvascular endothelium-dependent function (difference = −6.6%, 95%CI = −31.5%, 18.4%), endothelium independent function (difference = −10%, 95%CI = −95%, 75%) vasomotor function. The study has adequate power to identify known factors related to impaired microvascular endothelium-dependent function, such as smoking (difference = −42.5%, 95%CI = −79.0%, − 6.0%). Cases and controls have similar aerobic capacity (difference peak V̇O ₂ = −1.5, 95%CI = −4.8, 1.9 mL/kg/min), V̇O ₂ at anabolic threshold (difference = −1.0, 95%CI = −4.1, 2.1 mL/kg/min). Cases and controls have similar muscle histology, mitochondrial volume and density, and content of glycolytic, anerobic, tricarboxylic acid cycle and mitochondrial oxidative phosphorylation enzymes. RNAseq reveals no metabolic pathway gene dysregulation associated with GWI. Conclusions: Symptoms of GWI triggered by the physical and psychological trauma of war are unrelated to multiple peripheral vascular and muscle parameters. GWI patients should obtain a similar training effect from physical activity as those without GWI.
SN - 2730-664X
ER -