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Background <p>The rostral ventrolateral medulla (RVLM) is a critical vasomotor center that plays a pivotal role in the pathogenesis of hypertension. However, the involvement of circular RNAs (circRNAs) in this nucleus in blood pressure (BP) regulation remains incompletely understood.</p> Methods <p>In this study, we investigated functional circRNAs in the RVLM associated with hypertension and elucidated their underlying mechanisms using multiple experimental approaches, including RNA sequencing (RNA-seq), primary cell culture, and intra-RVLM microinjection.</p> Results <p>Our results revealed a significantly elevated level of the highly conserved circCdh7 in the RVLM of spontaneously hypertensive rats (SHRs). Downregulation of circCdh7 in the RVLM reduced neuronal excitability, sympathetic outflow, and BP in SHRs. Mechanistically, circCdh7 functioned as a sponge for miR-346. miR-346 knockdown largely abolished the inhibitory effects of circCdh7 suppression on RVLM astrogliosis and neuroinflammation. Furthermore, miR-346 was found to target Osmr. Overexpression of miR-346 attenuated RVLM astrogliosis and neuroinflammation, but these beneficial effects were abolished by Osmr overexpression.</p> Conclusions <p>Collectively, our findings demonstrate that elevated circCdh7 expression in the RVLM drives hypertension progression, with the circCdh7/miR-346/Osmr axis serving as a key regulatory mechanism. Targeting circCdh7 may represent a promising therapeutic strategy for hypertension.</p> Graphical abstract <p></p>

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CircCdh7 induces astrogliosis and neuroinflammation to trigger hypertensive effects in the rostral ventrolateral medulla

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月19日

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  • Shuai Zhang,
  • Tengteng Dai,
  • Bingjie Zhao,
  • Xueping Wang,
  • Linping Wang,
  • Lei Tong,
  • Qiangcheng Zeng,
  • Qing He,
  • Haili Zhang,
  • Dongshu Du

摘要

Background

The rostral ventrolateral medulla (RVLM) is a critical vasomotor center that plays a pivotal role in the pathogenesis of hypertension. However, the involvement of circular RNAs (circRNAs) in this nucleus in blood pressure (BP) regulation remains incompletely understood.

Methods

In this study, we investigated functional circRNAs in the RVLM associated with hypertension and elucidated their underlying mechanisms using multiple experimental approaches, including RNA sequencing (RNA-seq), primary cell culture, and intra-RVLM microinjection.

Results

Our results revealed a significantly elevated level of the highly conserved circCdh7 in the RVLM of spontaneously hypertensive rats (SHRs). Downregulation of circCdh7 in the RVLM reduced neuronal excitability, sympathetic outflow, and BP in SHRs. Mechanistically, circCdh7 functioned as a sponge for miR-346. miR-346 knockdown largely abolished the inhibitory effects of circCdh7 suppression on RVLM astrogliosis and neuroinflammation. Furthermore, miR-346 was found to target Osmr. Overexpression of miR-346 attenuated RVLM astrogliosis and neuroinflammation, but these beneficial effects were abolished by Osmr overexpression.

Conclusions

Collectively, our findings demonstrate that elevated circCdh7 expression in the RVLM drives hypertension progression, with the circCdh7/miR-346/Osmr axis serving as a key regulatory mechanism. Targeting circCdh7 may represent a promising therapeutic strategy for hypertension.

Graphical abstract