| Title |
Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway
|
|---|---|
| Published in |
GeroScience, May 2016
|
| DOI | 10.1007/s11357-016-9910-5 |
| Pubmed ID | |
| Authors |
Yan-qing Chen, Jing Zhao, Cheng-wei Jin, Yi-hui Li, Meng-xiong Tang, Zhi-hao Wang, Wei Zhang, Yun Zhang, Li Li, Ming Zhong |
| Abstract |
Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl- and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin II-induced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin II-induced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, Axl-Fc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor LY294002 abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 3% |
| Unknown | 33 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 18% |
| Student > Bachelor | 5 | 15% |
| Student > Master | 5 | 15% |
| Student > Doctoral Student | 4 | 12% |
| Researcher | 3 | 9% |
| Other | 4 | 12% |
| Unknown | 7 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 32% |
| Biochemistry, Genetics and Molecular Biology | 4 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Agricultural and Biological Sciences | 2 | 6% |
| Neuroscience | 2 | 6% |
| Other | 3 | 9% |
| Unknown | 10 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 May 2016.
All research outputs
#19,944,091
of 25,373,627 outputs
Outputs from GeroScience
#1,338
of 1,594 outputs
Outputs of similar age
#250,607
of 348,659 outputs
Outputs of similar age from GeroScience
#12
of 16 outputs
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