ArticleThe Journal of biological chemistry2010
Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Targeting calciphylaxis: the emergence of vitamin K as a potential treatment.Clinical kidney journal · 2026Review
- Spatial and Single-Cell Mapping Reveals Valvular Interstitial Cell and Macrophage Sex Differences in Calcific Aortic Valve Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Hormonal and Sex-Specific Regulation of Key Players in Fibro-Calcific Aortic Valve Disease.International journal of molecular sciences · 2025Article
- The relationship between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and abdominal aortic calcification in adults: a cross-sectional study.Frontiers in cardiovascular medicine · 2025Article
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- Understanding the Role of Sex Hormones in Cardiovascular Kidney Metabolic Syndrome: Toward Personalized Therapeutic Approaches.Journal of clinical medicine · 2024Review
- Roles of vitamin K‑dependent protein in biomineralization (Review).International journal of molecular medicine · 2024Review
- The Role of TAM Receptors in Bone.International journal of molecular sciences · 2023Review
- Serum DHEA and Testosterone Levels Associate Inversely With Coronary Artery Calcification in Elderly Men.The Journal of clinical endocrinology and metabolism · 2023Article
- Potential mechanisms linking high-volume exercise with coronary artery calcification.Heart (British Cardiac Society) · 2023Review
- Connectomic-genetic signatures in the cerebral small vessel disease.Neurobiology of disease · 2022Article
- Menopause, androgens, and cardiovascular ageing: a narrative review.Therapeutic advances in endocrinology and metabolism · 2022Review
- Ginsenoside Rb1 attenuates age-associated vascular impairment by modulating the Gas6 pathway.Pharmaceutical biology · 2021Article
- Vitamin KOpen heart · 2021Review
- Roles of Nuclear Receptors in Vascular Calcification.International journal of molecular sciences · 2021Review
- Regulatory Role of Sex Hormones in Cardiovascular Calcification.International journal of molecular sciences · 2021Review
- Sex-Stratified Gene Regulatory Networks Reveal Female Key Driver Genes of Atherosclerosis Involved in Smooth Muscle Cell Phenotype Switching.Circulation · 2021Article
- The Complex Interplay of Inflammation, Metabolism, Epigenetics, and Sex in Calcific Disease of the Aortic Valve.Frontiers in cardiovascular medicine · 2021Review
- Circadian rhythm disorder: a potential inducer of vascular calcification?Journal of physiology and biochemistry · 2020Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent epidemiological studies have found that androgen deficiency is associated with a higher incidence of cardiovascular disease in men. However, little is known about the mechanism underlying the cardioprotective effects of androgens. Here we show the inhibitory effects of testosterone on vascular calcification and a critical role of androgen receptor (AR)-dependent transactivation of growth arrest-specific gene 6 (Gas6), a key regulator of inorganic phosphate (P(i))-induced calcification of vascular smooth muscle cells (VSMC). Testosterone and nonaromatizable androgen dihydrotestosterone inhibited P(i)-induced calcification of human aortic VSMC in a concentration-dependent manner. Androgen inhibited P(i)-induced VSMC apoptosis, an essential process for VSMC calcification. The effects on VSMC calcification were mediated by restoration of P(i)-induced down-regulation of Gas6 expression and a subsequent reduction of Akt phosphorylation. These effects of androgen were blocked by an AR antagonist, flutamide, but not by an estrogen receptor antagonist, ICI 182,780. We then explored the mechanistic role of the AR in Gas6 expression and found an abundant expression of AR predominantly in the nucleus of VSMC and two consensus ARE sequences in the Gas6 promoter region. Dihydrotestosterone stimulated Gas6 promoter activity, and this effect was abrogated by flutamide and by AR siRNA. Site-specific mutation revealed that the proximal ARE was essential for androgen-dependent transactivation of Gas6. Furthermore, chromatin immunoprecipitation assays demonstrated ligand-dependent binding of the AR to the proximal ARE of Gas6. These results indicate that AR signaling directly regulates Gas6 transcription, which leads to inhibition of vascular calcification, and provides a mechanistic insight into the cardioprotective action of androgens.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.