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Phosphodiesterase 4D promotes angiotensin II-induced hypertension in mice via smooth muscle cell contraction

Tianfei Fan1, Yangfeng Hou1, Weipeng Ge1

  • 1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, China.

Communications Biology
|January 21, 2022
PubMed

Insights

This study shows that the PDE4D enzyme contributes to hypertension by affecting blood vessel contraction. Inhibiting PDE4D may offer a new treatment for hypertension.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Pharmacology

Background:

  • Hypertension is a prevalent chronic disease with increasing incidence, linked to cardio-cerebrovascular complications.
  • The cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway is implicated in cardiovascular diseases.
  • Phosphodiesterase 4 (PDE4) regulates PKA activity by hydrolyzing cAMP, but its role in hypertension is unclear.

Purpose of the Study:

  • To investigate the role of the PDE4-cAMP-PKA pathway in hypertension.
  • To determine if PDE4D influences angiotensin II (Ang II)-induced hypertension.

Main Methods:

  • Examined PDE4D expression in the aortas of Ang II-induced hypertensive mice.
  • Utilized Pde4d knockout mouse smooth muscle cells (SMCs) to assess its function.
  • Investigated the effects of PDE4D deficiency on the PKA-AMPK signaling pathway and SMC contraction.

Main Results:

  • PDE4D expression was upregulated in hypertensive mouse aortas.
  • Pde4d knockout in SMCs attenuated Ang II-induced hypertension, arterial thickening, fibrosis, and vasocontraction.
  • PDE4D deficiency activated the PKA-AMPK pathway, inhibiting MYPT1-MLC phosphorylation and reducing SMC contraction.

Conclusions:

  • PDE4D plays a significant role in Ang II-induced hypertension.
  • Targeting PDE4D may be a viable therapeutic strategy for hypertension.
  • The PDE4 inhibitor rolipram shows potential for hypertension treatment.

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