Aging increases p16INK4a expression in vascular smooth-muscle cells

2009 ◽  
Vol 30 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Luis Rodriguez-Menocal ◽  
Si M. Pham ◽  
Dania Mateu ◽  
Melissa St-Pierre ◽  
Yuntao Wei ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Cell Physiology ◽  
Post Injury ◽  
Aged Mice ◽  
Reverse Transcription Pcr ◽  
Serum Stimulation ◽  
Age Related

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 p16INK4a 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 p16INK4a (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 p16INK4a confirmed that aortas from aged mice contained more p16INK4a+ 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 p16INK4a in VSMC in both cultures and arteries. The increase in p16INK4a in the vasculature with aging may modify VSMC's response to post-injury stress and therefore accelerate the development of age-related cardiovascular diseases.

Age-related loss of SirT1 expression results in dysregulated human vascular smooth muscle cell function

2014 ◽  
Vol 307 (4) ◽  
pp. H533-H541 ◽  
Author(s):  
Anne Marie Thompson ◽  
Robert Wagner ◽  
Eva M. Rzucidlo
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Cellular Migration ◽  
Sirt1 Expression ◽  
Age Related ◽  
Significant Difference

Loss of vascular smooth muscle cell (VSMC) function is a hallmark of vascular disease. VSMCs become increasingly dysregulated, apoptotic, and senescent as we age. Sirtuin 1 (SirT1) is a deactylase that regulates substrates associated with stress mitigation, metabolism, and aging. Our aim was to examine the role of SirT1 in vascular aging and the function this protein plays in the context of cellular response to stress and senescence. We compared endogenous SirT1 expression in young and old human donors. Human VSMC (HuVSMC) from donors ranging in age from 12 to 88 ( n = 14) were isolated and cultured. In cultured HuVSMC the levels of endogenous SirT1 were examined by Western blot analysis. We found that endogenous SirT1 protein expression inversely correlated with donor age. Additionally, we demonstrated that age-related loss of SirT1 correlated in functional deficits, diminished stress response, reduced capacity for migration, and proliferation and increased senescence. Manipulation of SirT1 levels in young cells confirmed the role of SirT1 in cellular migration and proliferation capability. Furthermore, we demonstrated that age-related loss of SirT1 was associated with the induction of VSMC senescence. With correlation to symptomatic disease, we demonstrated a significant difference in SirT1 levels from HuVSMC isolated from aged arteries that were occluded with atherosclerotic lesions ( n = 7), compared with patent sections of the same artery. Having demonstrated that endogenous SirT1 is lost with age, which correlates with a loss of capacity for vascular repair, our data explain one of the molecular changes that occurs in the aged vasculature.

Age-related increase of stem marker expression influences vascular smooth muscle cell properties

2012 ◽  
Vol 224 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Amedeo Ferlosio ◽  
Gaetano Arcuri ◽  
Elena Doldo ◽  
Maria Giovanna Scioli ◽  
Sandro De Falco ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Age Related ◽  
Marker Expression ◽  
Related Increase

Involvement of Cyclooxygenase- and Lipoxygenase-Mediated Conversion of Arachidonic Acid in Controlling Human Vascular Smooth Muscle Cell Proliferation

1990 ◽  
Vol 63 (02) ◽  
pp. 291-297 ◽  
Author(s):  
Herm-Jan M Brinkman ◽  
Marijke F van Buul-Worteiboer ◽  
Jan A van Mourik
Keyword(s):  
Cell Proliferation ◽  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Muscle Cells ◽  
Smooth Muscle Cell Proliferation

SummaryWe observed that the growth of human umbilical arterysmooth muscle cells was inhibited by the phospholipase A2 inhibitors p-bromophenacylbromide and mepacrine. Thesefindings suggest that fatty acid metabolism might be integrated in the control mechanism of vascular smooth muscle cell proliferation. To identify eicosanoids possibly involved in this process, we studied both the metabolism of arachidonic acid of these cells in more detail and the effect of certain arachidonic acid metabolites on smooth muscle cells growth. We found no evidence for the conversion of arachidonic acid via the lipoxygenase pathway. In contrast, arachidonic acid was rapidly converted via the cyclooxy-genase pathway. The following metabolites were identified: prostaglandin E2 (PGE2), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), 12-hydroxyheptadecatrienoic acid (12-HHT) and 11-hydroxyeicosatetetraenoic acid (11-HETE). PGE2 was the major metabolite detected. Arachidonic acid metabolites were only found in the culture medium, not in the cell. After synthesis, 11-HETE was cleared from the culture medium. We have previously reported that PGE2 inhibits the serum-induced [3H]-thymidine incorporation of growth-arrested human umbilical artery smooth muscle cells. Here we show that also 11-HETEexerts this inhibitory property. Thus, our data suggeststhat human umbilical artery smooth muscle cells convert arachidonic acid only via the cyclooxygenase pathway. Certain metabolites produced by this pathway, including PGE2 and 11-HETE, may inhibit vascular smooth muscle cell proliferation.

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