Attenuated cell-cycle division protein 2 and elevated mitotic roles of polo-like kinase 1 characterize deficient myoblast fusion in peripheral arterial disease

Ferrari, Ricardo; Cong, Guangzhi; Chattopadhyay, Ansuman; Xie, Bowen; Assaf, Edwyn; Morder, Kristin; Calderon, Michael; Watkins, Simon C.; Sachdev, Ulka

doi:10.1016/j.bbrc.2022.03.161

Cited by 1 publication

(4 citation statements)

References 28 publications

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“…Ischemic myoblasts were harvested as described from ischemic calf muscles (ie, tibialis anterior). 8,12 Perfusion status was confirmed noninvasively. 13…”

Section: Methodsmentioning

confidence: 99%

“…Ischemic myoblasts were harvested as described from ischemic calf muscles (ie, tibialis anterior). 8,12 Perfusion status was confirmed noninvasively. 13 MuSCs were obtained using a modified sequential plating 14 and magnetic assisted cell sorting (#130-090-312; Miltenyi Biotech; MS Columns, #130-042-201) with anti-CD56-conjugated magnetic beads (Miltenyi Biotech; #130-050-401).…”

Section: Musc Harvest and Isolationmentioning

confidence: 99%

“…6 We showed that PAD MuSCs differentiate poorly, have elevated inflammatory and apoptotic caspase activity, and associate with fibrosis. [7][8][9] While apoptosis can promote fibrosis in heart tissue, 10 neither we nor others have evaluated Arterioscler Thromb Vasc Biol. 2023;43:2023-2029.…”

mentioning

confidence: 99%

“…We have shown our ability to study human MuSC in PAD. 7,8,11 We hypothesized that unsupervised transcriptomic analysis of these cells would provide an unbiased assessment of ischemic changes in human MuSCs, which drive repair. We also hypothesized that single-cell RNA sequencing (scRNA-seq) could further identify novel pathway targets such as ferroptosis to reduce myopathic injury from PAD.…”

mentioning

confidence: 99%

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Transcriptomic Profiling Identifies Ferroptosis-Related Gene Signatures in Ischemic Muscle Satellite Cells Affected by Peripheral Artery Disease—Brief Report

Tran,

Xie,

Assaf

et al. 2023

ATVB

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BACKGROUND: We hypothesized that transcriptomic profiling of muscle satellite cells in peripheral artery disease (PAD) would identify damage-related pathways contributing to skeletal muscle myopathy. We identified a potential role for ferroptosis—a form of programmed lytic cell death by iron-mediated lipid peroxidation—as one such pathway. Ferroptosis promotes myopathy in ischemic cardiac muscle but has an unknown role in PAD. METHODS: Muscle satellite cells from donors with PAD were obtained during surgery. cDNA libraries were processed for single-cell RNA sequencing using the 10X Genomics platform. Protein expression was confirmed based on pathways inferred by transcriptomic analysis. RESULTS: Unsupervised cluster analysis of over 25 000 cells aggregated from 8 donor samples yielded distinct cell populations grouped by a shared unique transcriptional fingerprint. Quiescent cells were diminished in ischemic muscle while myofibroblasts and apoptotic cells were prominent. Differential gene expression demonstrated a surprising increase in genes associated with iron transport and oxidative stress and a decrease in GPX4 (glutathione peroxidase 4) in ischemic PAD-derived cells. Release of the danger signal HMGB1 (high mobility group box-1) correlated with ferroptotic markers including surface transferrin receptor and were higher in ischemia. Furthermore, lipid peroxidation in muscle satellite cells was modulated by ferrostatin, a ferroptosis inhibitor. Histology confirmed iron deposition and lipofuscin, an inducer of ferroptosis in PAD-affected muscle. CONCLUSIONS: This is the first report documenting that genes known to be involved in ferroptosis are differentially expressed in human skeletal muscle affected by PAD. Targeting ferroptosis may be a novel therapeutic strategy to reduce PAD myopathy.

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“…Ischemic myoblasts were harvested as described from ischemic calf muscles (ie, tibialis anterior). 8,12 Perfusion status was confirmed noninvasively. 13…”

Section: Methodsmentioning

confidence: 99%

Section: Musc Harvest and Isolationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Transcriptomic Profiling Identifies Ferroptosis-Related Gene Signatures in Ischemic Muscle Satellite Cells Affected by Peripheral Artery Disease—Brief Report

Tran,

Xie,

Assaf

et al. 2023

ATVB

Self Cite

View full text Add to dashboard Cite

show abstract

Attenuated cell-cycle division protein 2 and elevated mitotic roles of polo-like kinase 1 characterize deficient myoblast fusion in peripheral arterial disease

Cited by 1 publication

References 28 publications

Transcriptomic Profiling Identifies Ferroptosis-Related Gene Signatures in Ischemic Muscle Satellite Cells Affected by Peripheral Artery Disease—Brief Report

Transcriptomic Profiling Identifies Ferroptosis-Related Gene Signatures in Ischemic Muscle Satellite Cells Affected by Peripheral Artery Disease—Brief Report

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