Extensive skeletal muscle cell mitochondriopathy distinguishes critical limb ischemia patients from claudicants Article Swipe
Terence E. Ryan
,
Dean J. Yamaguchi
,
Cameron A. Schmidt
,
Tonya N. Zeczycki
,
Saame Raza Shaikh
,
Patricia Brophy
,
Thomas D. Green
,
Michael D. Tarpey
,
Reema Karnekar
,
Emma J. Goldberg
,
Genevieve C. Sparagna
,
Maria J. Torres
,
Brian H. Annex
,
P. Darrell Neufer
,
Espen E. Spangenburg
,
Joseph M. McClung
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.123235
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.123235
The most severe manifestation of peripheral arterial disease (PAD) is critical limb ischemia (CLI). CLI patients suffer high rates of amputation and mortality; accordingly, there remains a clear need both to better understand CLI and to develop more effective treatments. Gastrocnemius muscle was obtained from 32 older (51-84 years) non-PAD controls, 27 claudicating PAD patients (ankle-brachial index [ABI] 0.65 ± 0.21 SD), and 19 CLI patients (ABI 0.35 ± 0.30 SD) for whole transcriptome sequencing and comprehensive mitochondrial phenotyping. Comparable permeabilized myofiber mitochondrial function was paralleled by both similar mitochondrial content and related mRNA expression profiles in non-PAD control and claudicating patient tissues. Tissues from CLI patients, despite being histologically intact and harboring equivalent mitochondrial content, presented a unique bioenergetic signature. This signature was defined by deficits in permeabilized myofiber mitochondrial function and a unique pattern of both nuclear and mitochondrial encoded gene suppression. Moreover, isolated muscle progenitor cells retained both mitochondrial functional deficits and gene suppression observed in the tissue. These findings indicate that muscle tissues from claudicating patients and non-PAD controls were similar in both their bioenergetics profile and mitochondrial phenotypes. In contrast, CLI patient limb skeletal muscles harbor a unique skeletal muscle mitochondriopathy that represents a potentially novel therapeutic site for intervention.
Related Topics
Concepts
Skeletal muscle
Mitochondrion
Transcriptome
Critical limb ischemia
Bioenergetics
Myocyte
Ankle
Gastrocnemius muscle
Progenitor cell
Biology
Ischemia
Internal medicine
Medicine
Cardiology
Pathology
Endocrinology
Gene expression
Cell biology
Gene
Stem cell
Arterial disease
Vascular disease
Biochemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1172/jci.insight.123235
- http://insight.jci.org/articles/view/123235/files/pdf
- OA Status
- gold
- Cited By
- 96
- References
- 62
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2899064175
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2899064175Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1172/jci.insight.123235Digital Object Identifier
- Title
-
Extensive skeletal muscle cell mitochondriopathy distinguishes critical limb ischemia patients from claudicantsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2018Year of publication
- Publication date
-
2018-11-01Full publication date if available
- Authors
-
Terence E. Ryan, Dean J. Yamaguchi, Cameron A. Schmidt, Tonya N. Zeczycki, Saame Raza Shaikh, Patricia Brophy, Thomas D. Green, Michael D. Tarpey, Reema Karnekar, Emma J. Goldberg, Genevieve C. Sparagna, Maria J. Torres, Brian H. Annex, P. Darrell Neufer, Espen E. Spangenburg, Joseph M. McClungList of authors in order
- Landing page
-
https://doi.org/10.1172/jci.insight.123235Publisher landing page
- PDF URL
-
https://insight.jci.org/articles/view/123235/files/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://insight.jci.org/articles/view/123235/files/pdfDirect OA link when available
- Concepts
-
Skeletal muscle, Mitochondrion, Transcriptome, Critical limb ischemia, Bioenergetics, Myocyte, Ankle, Gastrocnemius muscle, Progenitor cell, Biology, Ischemia, Internal medicine, Medicine, Cardiology, Pathology, Endocrinology, Gene expression, Cell biology, Gene, Stem cell, Arterial disease, Vascular disease, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
96Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 15, 2024: 18, 2023: 21, 2022: 13, 2021: 11Per-year citation counts (last 5 years)
- References (count)
-
62Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.equivalent | 113 |
| abstract_inverted_index.expression | 94 |
| abstract_inverted_index.functional | 152 |
| abstract_inverted_index.mortality; | 22 |
| abstract_inverted_index.paralleled | 85 |
| abstract_inverted_index.peripheral | 5 |
| abstract_inverted_index.progenitor | 147 |
| abstract_inverted_index.represents | 197 |
| abstract_inverted_index.sequencing | 74 |
| abstract_inverted_index.signature. | 120 |
| abstract_inverted_index.understand | 32 |
| abstract_inverted_index.phenotypes. | 182 |
| abstract_inverted_index.potentially | 199 |
| abstract_inverted_index.suppression | 156 |
| abstract_inverted_index.therapeutic | 201 |
| abstract_inverted_index.treatments. | 39 |
| abstract_inverted_index.accordingly, | 23 |
| abstract_inverted_index.bioenergetic | 119 |
| abstract_inverted_index.claudicating | 52, 100, 168 |
| abstract_inverted_index.phenotyping. | 78 |
| abstract_inverted_index.suppression. | 143 |
| abstract_inverted_index.Gastrocnemius | 40 |
| abstract_inverted_index.bioenergetics | 178 |
| abstract_inverted_index.comprehensive | 76 |
| abstract_inverted_index.intervention. | 204 |
| abstract_inverted_index.manifestation | 3 |
| abstract_inverted_index.mitochondrial | 77, 82, 89, 114, 130, 140, 151, 181 |
| abstract_inverted_index.permeabilized | 80, 128 |
| abstract_inverted_index.transcriptome | 73 |
| abstract_inverted_index.histologically | 109 |
| abstract_inverted_index.(ankle-brachial | 55 |
| abstract_inverted_index.mitochondriopathy | 195 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 98 |
| corresponding_author_ids | https://openalex.org/A5037990456 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 16 |
| corresponding_institution_ids | https://openalex.org/I186335123, https://openalex.org/I4210131376, https://openalex.org/I4210166371 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8600000143051147 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.97469587 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |