Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1

Bin Li, Wen-Wu Bai, Tao Guo, Zhen-Yu Tang, Xue-Jiao Jing, Ti-Chao Shan, Sen Yin, Ying Li, Fu Wang, Mo-Li Zhu, Jun-Xiu Lu, Yong-Ping Bai, Bo Dong (), Peng Li () and Shuang-Xi Wang ()
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Bin Li: Qilu Hospital of Shandong University
Wen-Wu Bai: Qilu Hospital of Shandong University
Tao Guo: Qilu Hospital of Shandong University
Zhen-Yu Tang: Qilu Hospital of Shandong University
Xue-Jiao Jing: Qilu Hospital of Shandong University
Ti-Chao Shan: Qilu Hospital of Shandong University
Sen Yin: Qilu Hospital of Shandong University
Ying Li: Central Hospital Affiliated to Shandong First Medical University
Fu Wang: Central Hospital Affiliated to Shandong First Medical University
Mo-Li Zhu: Xinxiang Medical University
Jun-Xiu Lu: Xinxiang Medical University
Yong-Ping Bai: Xinxiang Medical University
Bo Dong: Qilu Hospital of Shandong University
Peng Li: Xinxiang Medical University
Shuang-Xi Wang: Qilu Hospital of Shandong University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.

Date: 2024
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DOI: 10.1038/s41467-024-47327-z

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