ArticleThe Journal of biological chemistry2015
Leukotriene-C4 synthase, a critical enzyme in the activation of store-independent Orai1/Orai3 channels, is required for neointimal hyperplasia.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 35 citations in OpenAlex.
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Combination of Orai1 inhibitor CM5480 with specific therapy mitigates pulmonary hypertension and its cardiac dysfunction.JCI insight · 2025Article
- Too much of a good thing: The case of SOCE in cellular apoptosis.Cell calcium · 2023Review
- Article
- Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- Vascular Calcification Mechanisms: Updates and Renewed Insight into Signaling Pathways Involved in High Phosphate-Mediated Vascular Smooth Muscle Cell Calcification.Biomedicines · 2021Review
- ORAI1 CaFrontiers in cell and developmental biology · 2021Review
- The native ORAI channel trio underlies the diversity of CaNature communications · 2020Article
- Article
- ORAI channels in cellular remodeling of cardiorespiratory disease.Cell calcium · 2019Review
- Calcium signalling in T cells.Nature reviews. Immunology · 2019Review
- TRPC6 and TRPC4 Heteromultimerization Mediates Store Depletion-Activated NCX1 Reversal in Proliferative Vascular Smooth Muscle Cells.Channels (Austin, Tex.) · 2018Article
- Arachidonic acid-induced CaCancer cell international · 2018Article
- Article
- microRNA-612 is downregulated by platelet-derived growth factor-BB treatment and has inhibitory effects on vascular smooth muscle cell proliferation and migration via directly targeting AKT2.Experimental and therapeutic medicine · 2018Article
- Downregulation of Cavin-1 Expression via Increasing Caveolin-1 Degradation Prompts the Proliferation and Migration of Vascular Smooth Muscle Cells in Balloon Injury-Induced Neointimal Hyperplasia.Journal of the American Heart Association · 2017Article
- ORAI Calcium Channels.Physiology (Bethesda, Md.) · 2017Review
- Calcium Channels in Vascular Smooth Muscle.Advances in pharmacology (San Diego, Calif.) · 2017Review
- Cardiac Stim1 Silencing Impairs Adaptive Hypertrophy and Promotes Heart Failure Through Inactivation of mTORC2/Akt Signaling.Circulation · 2016Article
- Orai channel-mediated Ca2+ signals in vascular and airway smooth muscle.American journal of physiology. Cell physiology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Leukotriene-C4 synthase (LTC4S) generates LTC4 from arachidonic acid metabolism. LTC4 is a proinflammatory factor that acts on plasma membrane cysteinyl leukotriene receptors. Recently, however, we showed that LTC4 was also a cytosolic second messenger that activated store-independent LTC4-regulated Ca(2+) (LRC) channels encoded by Orai1/Orai3 heteromultimers in vascular smooth muscle cells (VSMCs). We showed that Orai3 and LRC currents were up-regulated in medial and neointimal VSMCs after vascular injury and that Orai3 knockdown inhibited LRC currents and neointimal hyperplasia. However, the role of LTC4S in neointima formation remains unknown. Here we show that LTC4S knockdown inhibited LRC currents in VSMCs. We performed in vivo experiments where rat left carotid arteries were injured using balloon angioplasty to cause neointimal hyperplasia. Neointima formation was associated with up-regulation of LTC4S protein expression in VSMCs. Inhibition of LTC4S expression in injured carotids by lentiviral particles encoding shRNA inhibited neointima formation and inward and outward vessel remodeling. LRC current activation did not cause nuclear factor for activated T cells (NFAT) nuclear translocation in VSMCs. Surprisingly, knockdown of either LTC4S or Orai3 yielded more robust and sustained Akt1 and Akt2 phosphorylation on Ser-473/Ser-474 upon serum stimulation. LTC4S and Orai3 knockdown inhibited VSMC migration in vitro with no effect on proliferation. Akt activity was suppressed in neointimal and medial VSMCs from injured vessels at 2 weeks postinjury but was restored when the up-regulation of either LTC4S or Orai3 was prevented by shRNA. We conclude that LTC4S and Orai3 altered Akt signaling to promote VSMC migration and neointima formation.
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.