title: Effects of donor age and proliferative aging on the phenotype stability of rat aortic smooth muscle cells.
abstract: Age-related effects of the vascular wall have been associated with several hemodynamic dysfunctions, including medial vascular calcification. Vascular aging has been traditionally addressed using proliferative senescence of vascular smooth muscle cells (VSMC) in vitro, which induces osteoblastic transition and favors calcification in vitro. In this work, we have analyzed the relationship between organismal aging and proliferative senescence by comparing the proliferative aging of VSMC obtained from young, mature, and old rats (2-, 12-, and 24-month cell lines [CL], respectively). VSMC proliferated to more than 100 cumulative population doublings (CPD) without evidence of proliferative senescence, most likely as a consequence of telomerase induction. The apoptosis rate increased with CPD in all three CL, but the oxidation status of the cells was not modified. The magnitude of all gene expression changes caused by CPD was higher than the magnitude of the changes caused by donor age: the expressions of VSMC markers α-actin and SM22α decreased, while the expressions of transcription factors Msx2 and Runx2 and of bone morphogenetic protein-2 increased. Treatment of the cells with 2 mmol/L Pi revealed that the intensity of the effect of CPD on calcium deposition was greater than the effect of donor age. In conclusion, the proliferative lifespan of VSMC magnifies the effect of donor age on the osteoblastic transition of VSMC, therefore suggesting that in vivo vascular aging changes can be less dramatic than what is shown by in vitro aging.
authors.affiliation: Department of Toxicology, University of Zaragoza, Zaragoza, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martín-Pardillos
authors.affiliation: Department of Toxicology, University of Zaragoza, Zaragoza, Spain sorribas@unizar.es.
authors.forename: Víctor
authors.initials: V
authors.lastname: Sorribas
keywords: Aging; proliferation; senescence; vascular calcification; vascular smooth muscle cells