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Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
Published on: June 3, 2019
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Cyclic nucleotide phosphodiesterase 1 and vascular aging
1Aab Cardiovascular Research Institute, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, U.S.A. chen_yan@urmc.rochester.edu.
Clinical Science (London, England : 1979)
|September 17, 2015
Summary
Phosphodiesterase 1 (PDE1) inhibition, using vinpocetine, reverses aging-related vascular smooth muscle cell dysfunction. This suggests PDE1A and PDE1C are key targets for treating vascular aging and associated diseases.
Area of Science:
- Cardiovascular Biology
- Aging Research
- Molecular Pharmacology
Background:
- Vascular smooth muscle cells (VSMCs) undergo phenotypic changes with aging, contributing to arterial remodeling.
- VSMC dysfunction, characterized by altered proliferation, migration, and inflammation, is central to age-associated vascular diseases.
- Cyclic nucleotide phosphodiesterases (PDEs) regulate crucial signaling pathways, and their dysregulation is implicated in disease.
Purpose of the Study:
- To investigate the role of PDE1 in VSMC senescence and age-related vascular dysfunction.
- To evaluate the therapeutic potential of PDE1 inhibition in reversing VSMC aging phenotypes.
Main Methods:
- Analysis of PDE1A and PDE1C mRNA levels in cultured senescent human VSMCs.
- Treatment of senescent VSMCs with vinpocetine, a PDE1 inhibitor.
- Assessment of aortic ring relaxation in premature aging mice (Ercc1(d/-)) treated with vinpocetine.
- Correlation analysis of PDE1A single nucleotide polymorphisms with human GWAS data for blood pressure and carotid intima-media thickness.
Main Results:
- PDE1A and PDE1C mRNA levels were significantly upregulated in senescent human VSMCs.
- Vinpocetine treatment reduced senescence markers in VSMCs and improved aortic ring relaxation in aging mice.
- PDE1A polymorphisms were significantly associated with diastolic blood pressure and carotid intima-media thickening in humans.
Conclusions:
- PDE1A and PDE1C are upregulated in aging VSMCs and contribute to vascular dysfunction.
- Inhibition of PDE1 activity with vinpocetine ameliorates cellular senescence and improves vascular function.
- PDE1 represents a promising therapeutic target for age-related vascular diseases.
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