2. Academic Validation
  3. MicroRNA-122-5p Aggravates Angiotensin II-Mediated Myocardial Fibrosis and Dysfunction in Hypertensive Rats by Regulating the Elabela/Apelin-APJ and ACE2-GDF15-Porimin Signaling

MicroRNA-122-5p Aggravates Angiotensin II-Mediated Myocardial Fibrosis and Dysfunction in Hypertensive Rats by Regulating the Elabela/Apelin-APJ and ACE2-GDF15-Porimin Signaling

  • J Cardiovasc Transl Res. 2022 Jun;15(3):535-547. doi: 10.1007/s12265-022-10214-3.
Jiawei Song  # 1 2 3,  Zhenzhou Zhang  # 1 2,  Zhaojie Dong 1 2,  Xinming Liu 1 2,  Ying Liu 1 2 3,  Xueting Li 1 2,  Yingle Xu 4,  Ying Guo 5,  Ning Wang 5,  Miwen Zhang 1 2,  Yihang Chen 1 2,  Haiyan Jin 6,  Jiuchang Zhong 7 8 9
Affiliations

Affiliations

  • 1 Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
  • 2 Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
  • 3 Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
  • 4 Department of Psychiatry &, School of Medicine, Shanghai Institute of HypertensionRuijin HospitalShanghai Jiao Tong University, Shanghai, China.
  • 5 Department of Geratology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
  • 6 Department of Psychiatry &, School of Medicine, Shanghai Institute of HypertensionRuijin HospitalShanghai Jiao Tong University, Shanghai, China. hyjin603@163.com.
  • 7 Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. jczhong@sina.com.
  • 8 Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. jczhong@sina.com.
  • 9 Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. jczhong@sina.com.
  • # Contributed equally.
PMID: 35174434 DOI: 10.1007/s12265-022-10214-3
Abstract

Hypertension is the leading risk factor for cardiovascular disorders. This study aimed to explore roles of MicroRNA (miR)-122-5p in hypertension. Angiotensin II (Ang II; 1.5 mg/kg/day) with an osmotic minipump was used to induce hypertensive rats pretreated by rAAV-miR-122-5p or rAAV-GFP, respectively. Notably, Ang II infusion caused marked increases in myocardial fibrosis, inflammation, oncosis, and oxidant injury in rats, which were aggravated by rAAV-miR-122-5p. RAAV-miR-122-5p exacerbated Ang II-mediated cardiac dysfunction and structural injury in hypertensive rats, with downregulated levels of apelin, elabela, ACE2, and GDF15, as well as upregulated expression of porimin and CTGF. In cultured rat cardiac fibroblasts, Ang II contributed to augmentation of cellular oncosis, migration, inflammation, and oxidative stress, with reduction of apelin, elabela, ACE2, and GDF15 levels, which were rescued by miR-122 inhibitor. In summary, miR-122-5p exacerbates myocardial fibrosis and dysfunction in hypertensive rats by modulating the elabela/apelin-ACE2-GDF15 signaling. MiR-122-5p has potential therapeutic significance for hypertension and hypertensive cardiac injury.

Keywords

Elabela; Hypertension; Myocardial fibrosis; Oncosis; miR-122-5p.

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