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

Previous studies have demonstrated that circulating microRNA (miR)-210 levels are ele-vated 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 mus-cle biopsies from CON (n = 20), intermittent claudication (IC) patients (n = 20), and criti-cal limb ischemia (CLI) patients (n = 20) were analyzed by high-resolution respirometry to measure mitochondrial respiration of permeabilized fibers. Samples were also ana-lyzed for miR-210 expression by real-time PCR. MiR-210 expression was significantly ele-vated 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 demon-strated 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 expres-sion of the miR-210 targets, cytochrome c oxidase assembly factor heme A: farnesyl-transferase (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. (Translational Research 2022; 246:66-77)