دورية أكاديمية
أعرض في EDS

Racial differences in the limb skeletal muscle transcriptional programs of patients with critical limb ischemia.

التفاصيل البيبلوغرافية
العنوان: Racial differences in the limb skeletal muscle transcriptional programs of patients with critical limb ischemia.
المؤلفون: Terwilliger ZS; Diabetes and Obesity Institute, East Carolina University, Brody Medical Center, Greenville, NC, USA.; Department of Physiology, East Carolina University, Brody Medical Center, Greenville, NC, USA., Ryan TE; Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA., Goldberg EJ; Diabetes and Obesity Institute, East Carolina University, Brody Medical Center, Greenville, NC, USA.; Department of Physiology, East Carolina University, Brody Medical Center, Greenville, NC, USA., Schmidt CA; Diabetes and Obesity Institute, East Carolina University, Brody Medical Center, Greenville, NC, USA.; Department of Physiology, East Carolina University, Brody Medical Center, Greenville, NC, USA., Yamaguchi DJ; Department of Cardiovascular Sciences, East Carolina University, Brody Medical Center, Greenville, NC, USA.; Division of Surgery, East Carolina University, Brody Medical Center, Greenville, NC, USA., Karnekar R; Diabetes and Obesity Institute, East Carolina University, Brody Medical Center, Greenville, NC, USA.; Department of Physiology, East Carolina University, Brody Medical Center, Greenville, NC, USA., Brophy P; Diabetes and Obesity Institute, East Carolina University, Brody Medical Center, Greenville, NC, USA., Green TD; Diabetes and Obesity Institute, East Carolina University, Brody Medical Center, Greenville, NC, USA.; Department of Physiology, East Carolina University, Brody Medical Center, Greenville, NC, USA., Zeczycki TN; Diabetes and Obesity Institute, East Carolina University, Brody Medical Center, Greenville, NC, USA.; Department of Biochemistry, East Carolina University, Brody Medical Center, Greenville, NC, USA., Mac Gabhann F; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA., Annex BH; Department of Medicine, Medical College of Georgia, Augusta, GA, USA.; Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA., McClung JM; Diabetes and Obesity Institute, East Carolina University, Brody Medical Center, Greenville, NC, USA.; Department of Physiology, East Carolina University, Brody Medical Center, Greenville, NC, USA.; Department of Cardiovascular Sciences, East Carolina University, Brody Medical Center, Greenville, NC, USA.
المصدر: Vascular medicine (London, England) [Vasc Med] 2021 Jun; Vol. 26 (3), pp. 247-258. Date of Electronic Publication: 2021 Mar 08.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: SAGE Publications Country of Publication: England NLM ID: 9610930 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-0377 (Electronic) Linking ISSN: 1358863X NLM ISO Abbreviation: Vasc Med Subsets: MEDLINE
أسماء مطبوعة: Publication: London : SAGE Publications
Original Publication: London, UK : Letchworth, Hertfordshire, UK : Arnold ; Turpin Distribution Services, c1996-
مواضيع طبية MeSH: Chronic Limb-Threatening Ischemia* , Peripheral Arterial Disease*/diagnosis , Peripheral Arterial Disease*/genetics , Peripheral Arterial Disease*/surgery, Adult ; Amputation, Surgical ; Critical Illness ; Humans ; Ischemia/diagnosis ; Ischemia/genetics ; Ischemia/surgery ; Limb Salvage ; Muscle, Skeletal/surgery ; Race Factors ; Risk Factors ; Treatment Outcome
مستخلص: Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease (PAD) and is characterized by high rates of morbidity and mortality. As with most severe cardiovascular disease manifestations, Black individuals disproportionately present with CLI. Accordingly, there remains a clear need to better understand the reasons for this discrepancy and to facilitate personalized therapeutic options specific for this population. Gastrocnemius muscle was obtained from White and Black healthy adult volunteers and patients with CLI for whole transcriptome shotgun sequencing (WTSS) and enrichment analysis was performed to identify alterations in specific Reactome pathways. When compared to their race-matched healthy controls, both White and Black patients with CLI demonstrated similar reductions in nuclear and mitochondrial encoded genes and mitochondrial oxygen consumption across multiple substrates, indicating a common bioenergetic paradigm associated with amputation outcomes regardless of race. Direct comparisons between tissues of White and Black patients with CLI revealed hemostasis, extracellular matrix organization, platelet regulation, and vascular wall interactions to be uniquely altered in limb muscles of Black individuals. Among traditional vascular growth factor signaling targets, WTSS revealed only Tie1 to be significantly altered from White levels in Black limb muscle tissues. Quantitative reverse transcription polymerase chain reaction validation of select identified targets verified WTSS directional changes and supports reductions in MMP9 and increases in NUDT4P1 and GRIK2 as unique to limb muscles of Black patients with CLI. This represents a critical first step in better understanding the transcriptional program similarities and differences between Black and White patients in the setting of amputations related to CLI and provides a promising start for therapeutic development in this population.
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معلومات مُعتمدة: R01 HL141325 United States HL NHLBI NIH HHS; R01 HL150003 United States HL NHLBI NIH HHS; R01 HL125695 United States HL NHLBI NIH HHS; R01 HL157659 United States HL NHLBI NIH HHS; R01 HL148590 United States HL NHLBI NIH HHS; R01 GM129074 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: critical limb ischemia (CLI); genetics; health disparities; ischemia; mitochondria; peripheral artery disease (PAD); skeletal muscle
تواريخ الأحداث: Date Created: 20210309 Date Completed: 20220309 Latest Revision: 20221207
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8227926
DOI: 10.1177/1358863X20983918
PMID: 33685287
قاعدة البيانات: MEDLINE
الوصف
تدمد:1477-0377
DOI:10.1177/1358863X20983918