Aging increases p16(INK4a) expression in vascular smooth-muscle cells

作者：Rodriguez Menocal Luis; Pham Si M; Mateu Dania; St Pierre Melissa; Wei Yuntao; Pestana Ivo; Aitouche Abdelouahab; Vazquez Padron Roberto I^*

来源：Bioscience Reports, 2010, 30(1): 11-18.

DOI：10.1042/BSR20080128

• aging
• aorta
• cell-cycle inhibitor
• p16(INK4a)
• restenosis
• vascular smooth-muscle cell

Alteration of VSMC (vascular smooth-muscle cell) physiology is associated with the development of atherosclerosis and restenosis. We hypothesize that aging up-regulates the expression of p16(INK4a) in VSMCs, which may increase the susceptibility of blood vessels to vascular occlusive diseases. Aortic VSMCs were obtained from young and aged mice. Cells from aged mice grew more slowly than those from their younger counterparts. Progression of cell cycle in response to serum stimulation was significantly inhibited in those cells with aging, as determined by FACS after propidium iodide staining. A significant up-regulation of p16(INK4a) (2.5-fold, P = 0.0012) was found in VSMC from aged animals using gene arrays. The up-regulation of this gene was further confirmed by quantitative RT-PCR (reverse transcription-PCR) and Western-blot experiments. Immunostaining for p16(INK4a) confirmed that aortas from aged mice contained more p16(INK4a ) SMA (smooth-muscle cell actin)( ) cells than aortas from young animals (26.79 /- 2.45 versus 7.06 /- 1.44, P = 0.00027, n = 4). In conclusion, we have shown that aging up-regulates the expression of p16(INK4a) in VSMC in both cultures and arteries. The increase in p16(INK4a) in the vasculature with aging may modify VSMC's response to post-injury stress and therefore accelerate the development of age-related cardiovascular diseases.

• 出版日期2010-2