Walking Training Increases microRNA-126 Expression and Muscle Capillarization in Patients with Peripheral Artery Disease

da Silva, Natan D., Andrade-Lima, Aluisio, Chehuen, Marcel R., Leicht, Anthony S., Brum, Patricia C., Oliveira, Edilamar M., Wolosker, Nelson, Pelozin, Bruno R.A., Fernandes, Tiago, and Forjaz, Cláudia L.M. (2023) Walking Training Increases microRNA-126 Expression and Muscle Capillarization in Patients with Peripheral Artery Disease. Genes, 14 (1). 101.

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Abstract

Patients with peripheral artery disease (PAD) have reduced muscle capillary density. Walking training (WT) is recommended for PAD patients. The goal of the study was to verify whether WT promotes angiogenesis in PAD-affected muscle and to investigate the possible role of miRNA-126 and the vascular endothelium growth factor (VEGF) angiogenic pathways on this adaptation. Thirty-two men with PAD were randomly allocated to two groups: WT (n = 16, 2 sessions/week) and control (CO, n = 16). Maximal treadmill tests and gastrocnemius biopsies were performed at baseline and after 12 weeks. Histological and molecular analyses were performed by blinded researchers. Maximal walking capacity increased by 65% with WT. WT increased the gastrocnemius capillary-fiber ratio (WT = 109 ± 13 vs. 164 ± 21 and CO = 100 ± 8 vs. 106 ± 6%, p < 0.001). Muscular expression of miRNA-126 and VEGF increased with WT (WT = 101 ± 13 vs. 130 ± 5 and CO = 100 ± 14 vs. 77 ± 20%, p < 0.001; WT = 103 ± 28 vs. 153 ± 59 and CO = 100 ± 36 vs. 84 ± 41%, p = 0.001, respectively), while expression of PI3KR2 decreased (WT = 97 ± 23 vs. 75 ± 21 and CO = 100 ± 29 vs. 105 ± 39%, p = 0.021). WT promoted angiogenesis in the muscle affected by PAD, and miRNA-126 may have a role in this adaptation by inhibiting PI3KR2, enabling the progression of the VEGF signaling pathway.

Item ID: 77272
Item Type: Article (Research - C1)
ISSN: 2073-4425
Keywords: intermittent claudication; physical exercise; capillarization; microRNA; VEGF
Copyright Information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Funders: FAPESP Brazil, CNPQ Brazil, CAPES-PROEX
Projects and Grants: FAPESP grant number 2015/13800-0, FAPESP grant number 2022/03138-2, CNPQ grant number 442507/2014-3, CNPQ grant number 304436/2018-6, CNPQ grant number 409629/2021-9, CAPES-PROEX grant number 0001
Date Deposited: 25 Jan 2023 01:59
FoR Codes: 42 HEALTH SCIENCES > 4207 Sports science and exercise > 420702 Exercise physiology @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified @ 50%
SEO Codes: 20 HEALTH > 2005 Specific population health (excl. Indigenous health) > 200599 Specific population health (excl. Indigenous health) not elsewhere classified @ 25%
20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 25%
13 CULTURE AND SOCIETY > 1306 Sport, exercise and recreation > 130601 Exercise @ 50%
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