ArticlePloS one2018
FTI-277 inhibits smooth muscle cell calcification by up-regulating PI3K/Akt signaling and inhibiting apoptosis.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Molecular mechanisms of programmed cell death in aortic dissection and advances in clinical translation.Molecular biology reports · 2026Review
- Role of Inositol Hexakisphosphate Kinases in Vascular Smooth Muscle Cell Calcification.International journal of molecular sciences · 2026Article
- Revealing the mechanisms of warfarin-induced vascular calcification through metabolomics and network toxicology.Frontiers in pharmacology · 2025Article
- Target analysis and identification of curcumin against vascular calcification.Scientific reports · 2024Article
- Article
- Potential Actions of Baicalein for Preventing Vascular Calcification of Smooth Muscle Cells In Vitro and In Vivo.International journal of molecular sciences · 2022Article
- Oxidative Stress Related to Plasmalemmal and Mitochondrial Phosphate Transporters in Vascular Calcification.Antioxidants (Basel, Switzerland) · 2022Review
- Phosphate Is a Cardiovascular Toxin.Advances in experimental medicine and biology · 2022Review
- Metabolomics of clinical samples reveal the treatment mechanism of lanthanum hydroxide on vascular calcification in chronic kidney disease.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2022Article
- Liraglutide Alleviates Diabetic Atherosclerosis through Regulating Calcification of Vascular Smooth Muscle Cells.Disease markers · 2022Article
- Globular adiponectin inhibits osteoblastic differentiation of vascular smooth muscle cells through the PI3K/AKT and Wnt/β-catenin pathway.Journal of molecular histology · 2021Article
- Article
- Acid sphingomyelinase promotes SGK1-dependent vascular calcification.Clinical science (London, England : 1979) · 2021Article
- Role of PI3K in the Progression and Regression of Atherosclerosis.Frontiers in pharmacology · 2021Review
- MicroRNA-342-5p activates the Akt signaling pathway by downregulating PIK3R1 to modify the proliferation and differentiation of vascular smooth muscle cells.Experimental and therapeutic medicine · 2020Article
- X-ray Micro-Computed Tomography: An Emerging Technology to Analyze Vascular Calcification in Animal Models.International journal of molecular sciences · 2020Review
- Intracellular matrix Gla protein promotes tumor progression by activating JAK2/STAT5 signaling in gastric cancer.Molecular oncology · 2020Article
- Vascular Calcification-New Insights Into Its Mechanism.International journal of molecular sciences · 2020Review
- [Daxx overexpression inhibits AngⅡ-induced proliferation and migration in vascular smooth muscle cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- Interactive and Multifactorial Mechanisms of Calcific Vascular and Valvular Disease.Trends in endocrinology and metabolism: TEM · 2019Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundVascular calcification is associated with increased cardiovascular morbidity and mortality in patients with atherosclerosis, diabetes and chronic kidney disease. However, no viable treatments for this condition have been identified. This study aimed to determine whether farnesyl transferase inhibitors (FTIs) can reduce vascular calcification and the mechanism by which this reduction occurs.
resultsWe demonstrate that FTI-277 significantly inhibits phosphate-induced mineral deposition by vascular smooth muscle cells (VSMC) in vitro, prevents VSMC osteogenic differentiation, and increases mRNA expression of matrix Gla protein (MGP), an inhibitor of mineralization. FTI-277 increases Akt signaling in VSMC in short-term serum-stimulation assays and in long-term mineralization assays. In contrast, manumycin A has no effect on Akt signaling or mineralization. Co-incubation of VSMC with FTI-277 and SH6 (an Akt inhibitor) significantly reduces the inhibitory effect of FTI-277 on mineralization, demonstrating that FTI-277 inhibits calcification by activating Akt signaling. Over-expression of the constitutively active p110 sub-unit of PI3K in VSMC using adenovirus activates Akt, inhibits mineralization, suppresses VSMC differentiation and significantly enhances MGP mRNA expression. FTI-277 also inhibits phosphate-induced activation of caspase 3 and apoptosis of VSMC, and these effects are negated by co-incubation with SH6. Finally, using an ex vivo model of vascular calcification, we demonstrate that FTI-277 inhibits high phosphate-induced mineralization in aortic rings derived from rats with end-stage renal failure.
conclusionsTogether, these results demonstrate that FTI-277 inhibits VSMC mineral deposition by up-regulating PI3K/Akt signaling and preventing apoptosis, suggesting that targeting farnesylation, or Akt specifically, may have therapeutic potential for the prevention of vascular calcification.
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