Telmisartan Modulates Exercise Responses in Peripheral Artery Disease: Analyses of Skeletal Muscle from the TELEX Trial
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PROVIDER: PRJNA1211515 | ENA |
REPOSITORIES: ENA
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Project description: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.
2025-08-27 | GSE287158 | GEO
Project description:Objective – Telmisartan, an angiotensin II type 1 (AT1) receptor blocker, and amlodipine, a calcium channel blocker, are antihypertensive agents clinically used as monotherapy or in combination. They exert beneficial cardiovascular effects independently of blood pressure lowering and classic mechanisms of action. In this study, we investigate molecular mechanisms responsible for the off-target effects of telmisartan and telmisartan-amlodipine in endothelial cells (EC), using an unbiased approach. Approach and Results – In human umbilical vein endothelial cells, microarray analysis of gene expression followed by pathway enrichment analysis and qRT-PCR validation revealed that telmisartan modulates the expression of key genes responsible for cell cycle progression and apoptosis. Amlodipine’s effect was similar to control. EC exposed to telmisartan, but not amlodipine, losartan or valsartan, exhibited a dose-dependent impairment of cell growth and failed to enter the S-phase of the cell cycle. Similarly, telmisartan inhibited proliferation in COS-7 cells lacking the AT1 receptor. In telmisartan-treated EC, phosphorylation and activation of Akt as well as MDM2 was reduced, leading to accumulation of p53 in the nucleus, where it represses the transcription of cell cycle promoting genes. Phosphorylation of GSK3β was also reduced, resulting in rapid proteolytic turnover of CyclinD1. Telmisartan induced downregulation of proapoptotic genes and protected EC from serum starvation- and 7-ketocholesterol-induced apoptosis. Conclusions – Telmisartan exerts antiproliferative and antiapoptotic effects in EC. This may account for the improved endothelial dysfunction observed in the clinical setting.
2013-05-14 | GSE42808 | GEO
Project description:To identify potential and novel target genes responsive to the anticancer effect in telmisartan-treated gynecological cancer cells, we examined the global changes in gene expression in HHUA endometrial cancer cells after treatment with telmisartan.
2012-03-22 | GSE36654 | GEO
Project description:Objective M-bM-^@M-^S Telmisartan, an angiotensin II type 1 (AT1) receptor blocker, and amlodipine, a calcium channel blocker, are antihypertensive agents clinically used as monotherapy or in combination. They exert beneficial cardiovascular effects independently of blood pressure lowering and classic mechanisms of action. In this study, we investigate molecular mechanisms responsible for the off-target effects of telmisartan and telmisartan-amlodipine in endothelial cells (EC), using an unbiased approach. Approach and Results M-bM-^@M-^S In human umbilical vein endothelial cells, microarray analysis of gene expression followed by pathway enrichment analysis and qRT-PCR validation revealed that telmisartan modulates the expression of key genes responsible for cell cycle progression and apoptosis. AmlodipineM-bM-^@M-^Ys effect was similar to control. EC exposed to telmisartan, but not amlodipine, losartan or valsartan, exhibited a dose-dependent impairment of cell growth and failed to enter the S-phase of the cell cycle. Similarly, telmisartan inhibited proliferation in COS-7 cells lacking the AT1 receptor. In telmisartan-treated EC, phosphorylation and activation of Akt as well as MDM2 was reduced, leading to accumulation of p53 in the nucleus, where it represses the transcription of cell cycle promoting genes. Phosphorylation of GSK3M-NM-2 was also reduced, resulting in rapid proteolytic turnover of CyclinD1. Telmisartan induced downregulation of proapoptotic genes and protected EC from serum starvation- and 7-ketocholesterol-induced apoptosis. Conclusions M-bM-^@M-^S Telmisartan exerts antiproliferative and antiapoptotic effects in EC. This may account for the improved endothelial dysfunction observed in the clinical setting. HUVEC were treated with 100 M-BM-5mol/L telmisartan or 5 M-BM-5mol/L amlodipine or both in dimethyl sulfoxide (DMSO) or an equivalent volume of DMSO alone, as control, for 24 hours. Microarray analysis was carried out on two biological replicates per group (total of six samples). See PROTOCOL section for experimental details.
2013-05-14 | E-GEOD-42808 | biostudies-arrayexpress
Project description:Bone marrow-derived progenitor cells are under investigation for cardiovascular repair, but may be altered by disease. We identified 82 differentially expressed genes in CD133+ cells from patients with coronary artery disease (CAD) versus controls, of which 59 were found to be up-regulated and 23 down-regulated. These genes were found to be involved in carbohydrate metabolism, cellular development and signaling, molecular transport and cell differentiation. Following completion of an exercise program, gene expression patterns resembled those of controls in 7 of 10 patients. Blood sampled from 4 healthy subjects (H), and from 10 patients with coronary artery disease at baseline (A) and after 3 months (B) of exercise.
2010-12-17 | E-GEOD-18608 | biostudies-arrayexpress
Project description:To identify potential and novel target genes responsive to the anticancer effect in telmisartan-treated gynecological cancer cells, we examined the global changes in gene expression in HHUA endometrial cancer cells after treatment with telmisartan. Gene expression profile in HHUA endometrial cancer cells treated with telmisartan
2012-03-22 | E-GEOD-36654 | biostudies-arrayexpress
Project description:LPS and Telmisartan co-treatment of microglial BV2 cells.
2018-07-02 | GSE108669 | GEO
Project description:LPS, Telmisartan and GW9662 co-treatment of microglial BV2 cells.
2018-07-02 | GSE108670 | GEO
Project description:Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor antagonist and a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, reportedly has beneficial effects on insulin sensitivity. We studied the effects of telmisartan on the adipose tissue macrophage phenotype in high fat-fed mice. Telmisartan was administered for 5 weeks to high fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in epididymal fat tissues were examined. Insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight and adipocyte size without affecting the amount of food intake. Telmisartan treatment reduced the number of CD11c-positive cells and crown-like structures. Telmisartan reduced the mRNA expressions of M1 macrophage markers, such as TNF-alpha and IL-6, and increased the expression of M2 markers, such as IL-10 and Mgl2. The reduction of M1 macrophage markers, as well as the increased gene expression of M2 markers especially IL-10, is a possible mechanism for the improvement of insulin sensitivity by telmisartan.
2010-01-23 | GSE19954 | GEO
Project description:Effect of Disease and Exercise in Skeletal Muscle of Patients with Peripheral Artery Disease
| PRJNA454312 | ENA