scholarly journals AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells

2018 ◽  
Author(s):  
Jun‑Kun Zhan ◽  
Yan‑Jiao Wang ◽  
Shuang Li ◽  
Yi Wang ◽  
Pan Tan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Replicative Senescence ◽  
Muscle Cells ◽  
Mtor Pathway

scholarly journals Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway

2015 ◽  
Vol 35 (3) ◽  
pp. 1151-1166 ◽  
Author(s):  
Cheng-wei Jin ◽  
Hui Wang ◽  
Yan-qing Chen ◽  
Meng-xiong Tang ◽  
Guan-qi Fan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Vascular Smooth Muscle Cells ◽  
Cellular Senescence ◽  
Replicative Senescence ◽  
Muscle Cells ◽  
Specific Protein ◽  
Foxo Signaling Pathway

Background/Aims: Growth arrest-specific protein 6 (Gas6) is a cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix. Previous studies have confirmed that Gas6 is involved in certain pathophysiological processes of the cardiovascular system through binding to its receptor, Axl. In the present study, we investigated the role of Gas6 in cellular senescence and explored the mechanisms underlying its activity. Methods: We used vascular smooth muscle cells (VSMCs) to create two cellular senescence models, one for replicative senescence (RS) and one for induced senescence (IS), to test the hypothesis that Gas6 delays senescence. Results: Gas6-treated cells appear relatively younger compared with non-Gas6-treated cells. In particular, Gas6-treated cells displayed decreased staining for SA-β-Gal, fewer G1 phase cells, and decreased levels of p16INK4a and p21Cip1 expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes. Furthermore, in both the IS and RS models with Gas6 treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased following PI3K inhibition by LY294002. Conclusion: Gas6/Axl signaling is essential for delaying the cellular senescence process regulated by the PI3K/Akt/FoxO signaling pathway.

Replicative senescence of vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transition

2009 ◽  
Vol 297 (5) ◽  
pp. H1673-H1684 ◽  
Author(s):  
Ritsuko Nakano-Kurimoto ◽  
Koji Ikeda ◽  
Maki Uraoka ◽  
Yusuke Nakagawa ◽  
Kotaro Yutaka ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Type I Collagen ◽  
Replicative Senescence ◽  
Muscle Cells ◽  
Type I ◽  
Medial Calcification

Medial artery calcification, which does not accompany lipid or cholesterol deposit, preferentially occurs in elderly population, but its underlying mechanisms remain unclear. In the present study, we investigated the potential role of senescent vascular smooth muscle cells (VSMCs) in the formation of senescence-associated medial calcification. Replicative senescence was induced by the extended passages (until passages 11–13) in human primary VSMCs, and cells in early passage ( passage 6) were used as control young cells. VSMC calcification was markedly enhanced in the senescent cells compared with that in the control young cells. We identified that genes highly expressed in osteoblasts, such as alkaline phosphatase (ALP) and type I collagen, were significantly upregulated in the senescent VSMCs, suggesting their osteoblastic transition during the senescence. Knockdown of either ALP or type I collagen significantly reduced the calcification in the senescent VSMCs. Of note, runt-related transcription factor-2 (RUNX-2), a core transcriptional factor that initiates the osteoblastic differentiation, was also upregulated in the senescent VSMCs. Knockdown of RUNX-2 significantly reduced the ALP expression and calcification in the senescent VSMCs, suggesting that RUNX-2 is involved in the senescence-mediated osteoblastic transition. Furthermore, immunohistochemistry of aorta from the klotho−/− aging mouse model demonstrated in vivo emergence of osteoblast-like cells expressing RUNX-2 exclusively in the calcified media. We also found that statin and Rho-kinase inhibitor effectively reduced the VSMC calcification by inhibiting Pi-induced apoptosis and potentially enhancing matrix Gla protein expression in the senescent VSMCs. These findings strongly suggest an important role of senescent VSMCs in the pathophysiology of senescence-associated medial calcification, and the inhibition of osteoblastic transition could be a new therapeutic approach for the prevention of senescence-associated medial calcification.

scholarly journals A comparison of replicative senescence and doxorubicin-induced premature senescence of vascular smooth muscle cells isolated from human aorta

2013 ◽  
Vol 15 (1) ◽  
pp. 47-64 ◽  
Author(s):  
Anna Bielak-Zmijewska ◽  
Maciej Wnuk ◽  
Dorota Przybylska ◽  
Wioleta Grabowska ◽  
Anna Lewinska ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Replicative Senescence ◽  
Muscle Cells ◽  
Human Aorta ◽  
Premature Senescence

Intracellular and exosomal microRNAome profiling of human vascular smooth muscle cells during replicative senescence

2021 ◽  
Vol 321 (4) ◽  
pp. H770-H783
Author(s):  
Diem Duong Ngoc Nguyen ◽  
Shamsul Mohd Zain ◽  
Mohd Hamzah Kamarulzaman ◽  
Teck Yew Low ◽  
William M. Chilian ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cellular Senescence ◽  
Crucial Role ◽  
Replicative Senescence ◽  
Muscle Cells ◽  
Vascular Aging ◽  
Exosomal Mirna

This is the first study on intracellular and exosomal miRNA profiling on human vascular smooth muscle cells during replicative senescence. Specific dysregulated sets of miRNAs were identified from human vascular smooth muscle cells. Hsa-miR-155-5p was significantly downregulated in both intracellular and exosomal hVSMCs, suggesting its crucial role in cellular senescence. Hsa-miR-155-5p might be the mediator in linking cellular senescence to vascular aging and atherosclerosis.

Sign in / Sign up

Export Citation Format

Share Document