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Telmisartan Modulates Exercise Responses in Peripheral Artery Disease: Analyses of Skeletal Muscle from the TELEX Trial

ABSTRACT: Background: In people with peripheral artery disease (PAD), the TELEX randomized clinical trial tested whether telmisartan (TEL), with or without exercise, significantly improved 6-minute walk distance at 6-month follow-up, compared to placebo (PLA). Objectives: The present study analyzed the effects of TEL on exploratory outcomes of muscle cellular and molecular characteristics. Methods: Baseline and 6-month follow-up muscle biopsies were obtained from 13 participants with PAD in the TELEX trial randomized to exercise + TEL or exercise + PLA. Immunohistochemistry was used to assess measures including myofiber cross-sectional area and satellite cell content, and the GeoMx digital spatial profiling system was used for transcriptomic analyses of alpha-smooth muscle actin (α-SMA)-positive and α-SMA-negative cells (primarily myofibers). Results: Myofiber cross-sectional area (CSA) and the number of satellite cells associated with Type II myofibers were significantly increased in the exercise + TEL group relative to exercise + PLA (p = 0.038 and p = 0.031, respectively). Among participants undergoing supervised exercise, those randomized to TEL had up-regulated N-linked glycosylation and down-regulated Ras signaling pathways in α-SMA-positive cells, compared to PLA. In α-SMA-negative cells, participants randomized to TEL showed up-regulated PPARγ activation-related pathways, including NO-cGMP-PKG signaling, and fatty acid oxidation. TEL also significantly reduced myostatin expression (adj. p = 0.0097) relative to PLA in α-SMA-negative cells. Conclusions: Overall, these findings suggest that TEL may regulate the effects of exercise on muscle in individuals with PAD by reducing myostatin expression, increasing myofiber size, and increasing activation of PPARγ.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE287158 | GEO | 2025/08/27

REPOSITORIES: GEO

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Telmisartan Modulates Exercise Responses in Peripheral Artery Disease: Analyses of Skeletal Muscle from the TELEX Trial

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