VSMCs (vascular smooth muscle cells) play critical roles in arterial remodelling with aging, hypertension and atherosclerosis. VSMCs exist in diverse phenotypes and exhibit phenotypic plasticity, e.g. changing from a quiescent/contractile phenotype to an active myofibroblast-like, often called ‘synthetic’, phenotype. Synthetic VSMCs are able to proliferate, migrate and secrete ECM (extracellular matrix) proteinases and ECM proteins. In addition, they produce pro-inflammatory molecules, providing an inflammatory microenvironment for leucocyte penetration, accumulation and activation. The aging VSMCs have also shown changes in cellular phenotype, responsiveness to contracting and relaxing mediators, replicating potential, matrix synthesis, inflammatory mediators and intracellular signalling. VSMC dysfunction plays a key role in age-associated vascular remodelling. Cyclic nucleotide PDEs (phosphodiesterases), by catalysing cyclic nucleotide hydrolysis, play a critical role in regulating the amplitude, duration and compartmentalization of cyclic nucleotide signalling. Abnormal alterations of PDEs and subsequent changes in cyclic nucleotide homoeostasis have been implicated in a number of different diseases. In the study published in the latest issue of Clinical Science, Bautista Niño and colleagues have shown that, in cultured senescent human VSMCs, PDE1A and PDE1C mRNA levels are significantly up-regulated and inhibition of PDE1 activity with vinpocetine reduced cellular senescent makers in senescent VSMCs. Moreover, in the premature aging mice with genomic instability (Ercc1d/−), impaired aortic ring relaxation in response to SNP (sodium nitroprusside), an NO (nitric oxide) donor, was also largely improved by vinpocetine. More interestingly, using data from human GWAS (genome-wide association studies), it has been found that PDE1A single nucleotide polymorphisms is significantly associated with diastolic blood pressure and carotid intima–media thickening, two hallmarks of human vascular dysfunction in aging. These findings establish a strong relationship between PDE1 expression regulation and vascular abnormalities in aging.
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Commentary|
October 13 2015
Cyclic nucleotide phosphodiesterase 1 and vascular aging
Chen Yan
*Aab Cardiovascular Research Institute, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, U.S.A.
Correspondence: Dr Chen Yan (email [email protected]).
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Publisher: Portland Press Ltd
Received:
August 25 2015
Revision Received:
September 10 2015
Accepted:
September 14 2015
Accepted Manuscript online:
September 14 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2015 Authors; published by Portland Press Limited
2015
Clin Sci (Lond) (2015) 129 (12): 1077–1081.
Article history
Received:
August 25 2015
Revision Received:
September 10 2015
Accepted:
September 14 2015
Accepted Manuscript online:
September 14 2015
Connected Content
A commentary has been published:
Phosphodiesterase 1 regulation is a key mechanism in vascular aging
Citation
Chen Yan; Cyclic nucleotide phosphodiesterase 1 and vascular aging. Clin Sci (Lond) 1 December 2015; 129 (12): 1077–1081. doi: https://doi.org/10.1042/CS20150605
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