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Azilsartan ameliorates angiotensin Ⅱ-induced skeletal muscle atrophy via AT1R-mediated PI3K/AKT/FOXO3a signaling pathway
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Yan CUI1, 2, Wei-Peng LI2, Yue YU2, Peng LU3, Jia-Wen LI4, Can ZHAO2, Jin-Shui XU5, Zheng-Kai SHEN5, ✉, Xiang LU2, ✉, Wei GAO4, ✉
Journal of Geriatric Cardiology | 2026, 23(9) : 609 - 621
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Journal of Geriatric Cardiology | 2026, 23(9): 609-621
• RESEARCH ARTICLE •
Azilsartan ameliorates angiotensin Ⅱ-induced skeletal muscle atrophy via AT1R-mediated PI3K/AKT/FOXO3a signaling pathway
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Yan CUI1, 2, Wei-Peng LI2, Yue YU2, Peng LU3, Jia-Wen LI4, Can ZHAO2, Jin-Shui XU5, Zheng-Kai SHEN5, ✉, Xiang LU2, ✉, Wei GAO4, ✉
Affiliations
  • 1.Department of Geriatrics, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China
  • 2.Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
  • 3.Department of Geriatrics, the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, China
  • 4.Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
  • 5.Jiangsu Province Center for Disease Control and Prevention, Nanjing, China
About Author:

*

The authors contributed equally to this manuscript

Published: 2026-09-28 doi: 10.26599/1671-5411.2026.09.008
Outline
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Background

Sarcopenia is a progressive age-related skeletal muscle disorder characterized by the loss of muscle mass, strength, and physical performance. Increasing evidence suggests that activation of the renin-angiotensin system (RAS) contributes to muscle wasting through promotion of protein degradation and impairment of anabolic signaling. Azilsartan (AZL), a highly selective angiotensin Ⅱ type 1 receptor (AT1R) blocker, has demonstrated pleiotropic effects beyond blood pressure control. However, its effects on skeletal muscle atrophy and the underlying mechanisms remain incompletely understood.

Methods

We combined a prospective observational study with mechanistic investigations in animal and cellular models. Older adults with hypertension and sarcopenia received AZL (40 mg/day) or other antihypertensive therapies for 6 months, and muscle strength, gait speed, and appendicular skeletal muscle mass were assessed. Moreover, Ang Ⅱ-induced skeletal muscle atrophy models were established in mice and C2C12 myotubes to evaluate the effects of AZL on muscle morphology and signaling pathways.

Results

AZL treatment was associated with significant improvements in handgrip strength, gait speed, and appendicular skeletal muscle mass in older hypertensive patients. In experimental models, Ang Ⅱ induced skeletal muscle dysfunction and atrophy, characterized by reduced exercise capacity, decreased grip strength, and muscle fiber loss, were attenuated by AZL treatment. Mechanistically, AZL restored PI3K/Akt/FOXO3a signaling and suppressed the expression of the muscle-specific ubiquitin ligases Atrogin-1 and MuRF1. The protective effects of AZL were abolished by the AT1R agonist TRV120027 in both in vivo and in vitro models and were further attenuated by the PI3K inhibitor LY294002 in C2C12 myotubes.

Conclusions

AZL attenuates Ang Ⅱ-induced skeletal muscle atrophy through AT1R blockade and subsequent activation of PI3K/Akt/FOXO3a signaling, thereby suppressing ubiquitin-proteasome system-mediated muscle protein degradation. These findings provide mechanistic and translational evidence supporting the potential of AZL as a therapeutic strategy for preserving skeletal muscle health in older adults with hypertension.

Yan CUI, Wei-Peng LI, Yue YU, Peng LU, Jia-Wen LI, Can ZHAO, Jin-Shui XU, Zheng-Kai SHEN, Xiang LU, Wei GAO. Azilsartan ameliorates angiotensin Ⅱ-induced skeletal muscle atrophy via AT1R-mediated PI3K/AKT/FOXO3a signaling pathway. 老年心脏病杂志（英文）, 2026 , 23 (9) : 609 -621 . DOI: 10.26599/1671-5411.2026.09.008
Yan CUI, Wei-Peng LI, Yue YU, Peng LU, Jia-Wen LI, Can ZHAO, Jin-Shui XU, Zheng-Kai SHEN, Xiang LU, Wei GAO. Azilsartan ameliorates angiotensin Ⅱ-induced skeletal muscle atrophy via AT1R-mediated PI3K/AKT/FOXO3a signaling pathway[J]. Journal of Geriatric Cardiology, 2026 , 23 (9) : 609 -621 . DOI: 10.26599/1671-5411.2026.09.008
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Funding
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  • This work was supported by grants from the Jiangsu Commission of Health (No. LKZ2023005 to Wei Gao, No. LKM2023004 to Zheng-Kai Shen), the project of Zhongda Hospital Affiliated to Southeast University for cultivating academic talent (No. CZXM-GSPRC22 to Wei Gao), the Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Pairing Assistance Construction Funds (No. ZDLYG10 to Wei Gao), the Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Construction Funds (No. GSP-LCYJFH17 to Wei Gao), China Heart House-Chinese Cardiovascular Association HX fund (No. 2022-CCA-HX-082 to Wei Gao), Bethune Charitable Foundation (No. 2024020185BA to Wei Gao).
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Year 2026 volume 23 Issue 9
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Article Info
doi: 10.26599/1671-5411.2026.09.008
  • Online Date：2026-10-30
  • Published：2026-09-28
Article Data
Affiliations
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Funding
This work was supported by grants from the Jiangsu Commission of Health (No. LKZ2023005 to Wei Gao, No. LKM2023004 to Zheng-Kai Shen), the project of Zhongda Hospital Affiliated to Southeast University for cultivating academic talent (No. CZXM-GSPRC22 to Wei Gao), the Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Pairing Assistance Construction Funds (No. ZDLYG10 to Wei Gao), the Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Construction Funds (No. GSP-LCYJFH17 to Wei Gao), China Heart House-Chinese Cardiovascular Association HX fund (No. 2022-CCA-HX-082 to Wei Gao), Bethune Charitable Foundation (No. 2024020185BA to Wei Gao).
Affiliations
    1.Department of Geriatrics, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China
    2.Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
    3.Department of Geriatrics, the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, China
    4.Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
    5.Jiangsu Province Center for Disease Control and Prevention, Nanjing, China

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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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