Skeletal muscle MiR-210 expression is associated with mitochondrial function in peripheral artery disease patients

AHMED Ismaeel, E. M.M.A. FLETCHER, DIMITRIOS MISERLIS, MARISSA WECHSLER, EVLAMPIA PAPOUTSI, G. L.E.B. HAYNATZKI, ROBERT S. SMITH, WILLIAM T. BOHANNON, PANAGIOTIS KOUTAKIS

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies have demonstrated that circulating microRNA (miR)-210 levels are elevated in peripheral artery disease (PAD) patients. MiR-210 is known to be a negative regulator of mitochondrial respiration; however, the relationship between miR-210 and mitochondrial function has yet to be studied in PAD. We aimed to compare skeletal muscle miR-210 expression of PAD patients to non-PAD controls (CON) and to examine the relationship between miR-210 expression and mitochondrial function. Skeletal muscle biopsies from CON (n = 20), intermittent claudication (IC) patients (n = 20), and critical limb ischemia (CLI) patients (n = 20) were analyzed by high-resolution respirometry to measure mitochondrial respiration of permeabilized fibers. Samples were also analyzed for miR-210 expression by real-time PCR. MiR-210 expression was significantly elevated in IC and CLI muscle compared to CON (P = 0.008 and P < 0.001, respectively). Mitochondrial respiration of electron transport chain (ETC) Complexes II (P = 0.001) and IV (P < 0.001) were significantly reduced in IC patients. Further, CLI patients demonstrated significant reductions in respiration during Complexes I (state 2: P = 0.04, state 3: P = 0.003), combined I and II (P < 0.001), II (P < 0.001), and IV (P < 0.001). The expression of the miR-210 targets, cytochrome c oxidase assembly factor heme A: farnesyltransferase (COX10), and iron-sulfur cluster assembly enzyme (ISCU) were down-regulated in PAD muscle. MiR-210 may play a role in the cellular adaptation to hypoxia and may be involved in the metabolic myopathy associated with PAD.

Original languageEnglish (US)
Pages (from-to)66-77
Number of pages12
JournalTranslational Research
Volume246
DOIs
StatePublished - Aug 2022

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Physiology (medical)
  • Biochemistry, medical

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