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Updated: Sep 17, 2025

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Ang II-induced oscillation of clock genes can attenuate phenotypic transformation in vascular smooth muscle cells by

Conglan Ji1,2, Tao Ge3, Nan Wang2

  • 1School of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, China.

Chronobiology International
|July 4, 2025
PubMed

Insights

Clock genes Per1/Per2 regulate angiotensin II (Ang II) effects on vascular smooth muscle cells (VSMCs). A feedback loop involving AT1R-Per1/Per2 counteracts Ang II-induced VSMC transformation.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Chronobiology

Background:

  • Vascular smooth muscle cell (VSMC) phenotypic transformation is central to cardiovascular diseases.
  • Angiotensin II (Ang II) plays a critical role in regulating VSMC function.
  • The involvement of circadian clock genes in Ang II-mediated VSMC responses remains incompletely understood.

Purpose of the Study:

  • To investigate the role of clock genes Per1 and Per2 in Ang II-induced VSMC phenotypic transformation.
  • To elucidate the molecular mechanisms underlying this interaction.
  • To identify potential therapeutic targets for cardiovascular conditions.

Main Methods:

  • Primary rat VSMCs were treated with Ang II and various inhibitors.
  • Quantitative PCR and Western blotting were used to assess gene and protein expression (Per1, Per2, AT1R, p-CREB).
  • Cell viability, cell cycle, intracellular calcium ([Ca2+]i), and inositol trisphosphate (IP3) levels were measured.

Main Results:

  • Ang II induced Per1/Per2 mRNA expression at specific time points and altered protein levels.
  • Inhibitors of AT1R, PKC, PLC, IP3R, and calcium channels blocked Ang II's effects on Per1/Per2.
  • Ang II modulated p-CREB, IP3, and [Ca2+]i, with transient increases and long-term decreases.
  • Silencing Per1/Per2 exacerbated Ang II-induced VSMC proliferation.
  • A feedback loop between AT1R and Per1/Per2 was identified.

Conclusions:

  • Ang II triggers Per1/Per2 oscillations via the AT1R/PLC/Ca2+/PKC/p-CREB signaling pathway.
  • The AT1R-Per1/Per2 feedback loop acts as a crucial mechanism counteracting Ang II-driven VSMC phenotypic transformation.
  • Clock genes Per1/Per2 are key regulators of VSMC response to Ang II, offering potential therapeutic avenues.
Keywords:
Ang IIMLC20PKCcell proliferationnegative feedback loopvascular smooth muscle cells

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