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Piwi-interacting RNAs (piRNAs) as potential biomarkers and therapeutic targets for cardiovascular diseases


Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Increasing reports demonstrated that non-coding RNAs (ncRNAs) have been crucially involved in the development of CVDs. Piwi-interacting RNAs (piRNAs) are a novel cluster of small non-coding RNAs with strong uracil bias at the 5′ end and 2′-O-methylation at the 3′ end that are mainly present in the mammalian reproductive system and stem cells and serve as potential modulators of developmental and pathophysiological processes. Recently, piRNAs have been reported to be widely expressed in human tissues and can potentially regulate various diseases. Specifically, concomitant with the development of next-generation sequencing techniques, piRNAs have been found to be differentially expressed in CVDs, indicating their potential involvement in the occurrence and progression of heart diseases. However, the molecular mechanisms and signaling pathways involved with piRNA function have not been fully elucidated. In this review, we present the current understanding of the piRNAs from the perspectives of biogenesis, characteristics, biological function, and regulatory mechanisms, and highlight their potential roles and underlying mechanisms in CVDs, which will provide new insights into the potential applications of piRNAs in the clinical diagnosis, prognosis, and therapeutic strategies for heart diseases.

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Adipose-derived stem cells


Argonaute 2






Glucose-repressible alcohol dehydrogenase transcriptional effector


DNA methyltransferase


Cardiovascular diseases


CDK5 regulatory subunit-associated protein 1


Clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins


Chronic thromboembolic pulmonary hypertension


Double-stranded RNA


Endothelial cells


Heart failure


Histone 3 trimethylated on lysine 9


Long interspersed nuclear elements-1


Myocardial infarction


Activating transcription factor 7 interacting protein


Methyl CpG binding protein 2


Multiple myeloma


Mov10-like RISC complex RNA helicase 1


Mesenchymal stem cells


Non-coding RNAs




Pulmonary hypertension


Piwi-interacting RNAs


PiRNA-induced silence compounds


The type II arginine methyltransferasev


Quantitative PCR


RNA interference


RNA sequencing


SET domain-bifurcated histone lysine methyltransferase 1


Small interfering RNA


Small ubiquitin-like modifier


Transposable element


UORF downstream regions


Ubiquitin-like, containing PHD and RING finger domains 1


Proximal short open reading frames


WD repeat domain 77




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This work was supported by The National Natural Science Foundation of China (Grant No. 81870331, 31701208), The Natural Science Foundation of Shandong Province (Grant No. ZR2017MC067), and The Qingdao municipal science and technology bureau project (Grant No. 18-2-2-65-jch).

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ML, YY, and ZW collected materials and wrote the manuscript. TY and JW provided the idea. KW and TZ are responsible for the schematic diagram within this article. TY, LHHA, and XF helped with the final revision of the article. All authors reviewed the manuscript and approved the final manuscript.

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Correspondence to Tao Yu.

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Li, M., Yang, Y., Wang, Z. et al. Piwi-interacting RNAs (piRNAs) as potential biomarkers and therapeutic targets for cardiovascular diseases. Angiogenesis 24, 19–34 (2021).

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  • piRNAs
  • Cvds
  • PIWI proteins
  • ncRNAs
  • Therapy