Author ORCID Identifier
Myers - https://orcid.org/0000-0002-2934-2624
Pipinos - https://orcid.org/0000-0001-6873-6346
Document Type
Article
Publication Date
8-21-2020
Abstract
Peripheral artery disease (PAD), a severe atherosclerotic condition primarily of the elderly, afflicts 200 million individuals, worldwide, and is associated with lower extremity myopathy. Circulating markers of inflammation have been linked to risk and severity of PAD but the contribution of local inflammation to myopathy remains unknown. We evaluated, by ELISA, calf muscle of PAD patients (N = 23) and control subjects (N = 18) for local expression of inflammatory cytokines including Granulocyte/Monocyte Colony-Stimulating Factor (GM-CSF), Interleukin 17A (IL-17A), Interferon ϒ (IFN-ϒ), tumor necrosis factor α (TNF-α), and Interleukin 6 (IL-6). One or more of these cytokines were expressed in nineteen patients and 2 controls and coordinated expression of GM-CSF, IL-17A, IFN-ϒ, and TNF-α, a signature of activated, MHC Class II dependent autoreactive Th-cells, was unique to 11 patients. GM-CSF is the central driver of tissue-damaging myeloid macrophages. Patients with this cytokine signature had a shorter (P= 0.017) Claudication Onset Distance (17 m) compared with patients lacking the signature (102 m). Transforming Growth Factor β1 (TGFβ1) and Chemokine Ligand 5 (CCL5) were expressed coordinately in all PAD and control muscles, independently of GM-CSF, IL-17A, IFN-ϒ, TNF-α, or IL-6. TGFβ1 and CCL5 and their gene transcripts were increased in PAD muscle, consistent with increased age-associated inflammation in these patients. Serum cytokines were not informative of muscle cytokine expression. We have identified a cytokine profile of autoimmune inflammation in calf muscles of a significant proportion of claudicating PAD patients, in association with decreased limb function, and a second independent profile consistent with increased “inflammaging” in all PAD patients.
Journal Title
Translational Research
Volume
288
First Page
94
Last Page
108
Recommended Citation
Casale GP, Thompson JR, Carpenter LC, Kim J, Lackner TJ, Mietus CJ, Ha DM, Myers SA, Brunette KE, Li s, Shields C, Willcockson G, Pipinos II. Cytokine signature of inflammation mediated by autoreactive Th-cells, in calf muscle of claudicating patients with Fontaine stage II peripheral artery disease. Translational Research. 2021 Feb;228:94-108.https://doi.org/10.1016/j.trsl.2020.08.008
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
This is an Accepted Manuscript of an article published by Elsevier in Translational Research on [August 21, 2020], available online: https://doi.org/10.1016/j.trsl.2020.08.008