UNASSIGNED: Vascular smooth muscle cells (VSMCs) play critical roles in arterial remodeling with @entity1240 , @entity101 , and @entity731 . 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 VSMC cells are able to proliferate, migrate, and secrete extracellular matrix (ECM) proteinases and ECM proteins. In addition, they produce pro-inflammatory molecules, providing an inflammatory microenvironment for leukocyte penetration, accumulation and activation. The @entity1240 VSMCs have also shown changes in cellular phenotype, responsiveness to contracting and relaxing mediators, replicating potential, matrix synthesis, inflammatory mediators and intracellular signaling. @entity409 plays a key role in age-associated vascular remodeling. @entity8614 phosphodiesterases (PDEs), by catalyzing @entity8614 hydrolysis, play a critical role in regulating the amplitude, duration, and compartmentalization of @entity8614 signaling. Abnormal alterations of PDEs and subsequent changes of @entity8614 homeostasis have been implicated in a number of different diseases. In the study published in this issue, Nino et al have shown that in cultured senescent @entity1 VSMCs, @entity46976 and @entity45721 mRNA levels are sognificanly up-regulated and Inhibition of PDE1 activity with @entity53537 reduced cellular senescent makers in senescent VSMCs. Moreover, in the @entity1240 @entity19 with genomic instability ( @entity13139 (d/-)), impaired aortic ring relaxation in response to @entity1854 (SNP, a NO donor) was also largely improved by @entity53537 . More interestingly, using data from @entity1 Genome-Wide Association Studies (GWAS), it has been found that @entity46976 single nucleotide polymorphisms ( @entity4982 ) is significantly associated with diastolic blood pressure and carotid intima/media thickening, two hallmarks of @entity1 @entity455 in @entity1240 . These findings establish a strong relationship between PDE1 expression regulation and @entity455 in @entity1240 .

XXXX Phosphodiesterase 1 and Vascular Aging.

@entity1 :: ('9606', 'Species') :: ['human'] @entity46976 :: ('5136', 'Gene') :: ['PDE1A'] @entity455 :: ('MESH:D014652', 'Disease') :: ['vascular abnormalities', 'vascular dysfunction'] @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension'] @entity13139 :: ('13870(Tax:10090)', 'Gene') :: ['Ercc1'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity409 :: ('MESH:D008107', 'Disease') :: ['VSMC dysfunction'] @entity1854 :: ('MESH:D009599', 'Chemical') :: ['sodium nitroprusside'] @entity8614 :: ('D009712', 'Chemical') :: ['cyclic nucleotide', 'Cyclic nucleotide'] @entity4982 :: ('D009599', 'Chemical') :: ['SNP'] @entity1240 :: ('MESH:D019588', 'Disease') :: ['aging', 'premature aging'] @entity53537 :: ('MESH:C013983', 'Chemical') :: ['vinpocetine'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis'] @entity45721 :: ('5137', 'Gene') :: ['PDE1C']
@entity8614 :: (D009712,Chemical) :: ['Cyclic Nucleotide']
