ArticlePloS one2012
Cilostazol prevents endothelin-induced smooth muscle constriction and proliferation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Randomized control trial comparing the effect of cilostazol and aspirin on changes in carotid intima-medial thickness.Heart and vessels · 2019Trial
- Trial
- Treatment-Related Reversible Cerebral Vasoconstriction Syndrome.Journal of clinical medicine · 2024Review
- Recurrent reversible cerebral vasoconstriction syndrome and antiphospholipid syndrome.Acta neurologica Belgica · 2024Article
- Cilostazol regulates the expressions of endothelin-1 and endothelial nitric oxide synthase via activation of the p38 MAPK signaling pathway in HUVECs.Biomedical reports · 2022Article
- Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States.American journal of biomedical science & research · 2022Article
- A case of reversible cerebral vasoconstriction syndrome associated with anti-phospholipid antibody syndrome and systemic lupus erythematosus.eNeurologicalSci · 2021Article
- Long-Term Cilostazol Treatment and Predictive Factors on Outcomes of Endovascular Intervention in Patients with Diabetes Mellitus and Critical Limb Ischemia.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2020Article
- Endothelin-1 Mediates the Systemic and Renal Hemodynamic Effects of GPR81 Activation.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Pharmacological Potential of Cilostazol for Alzheimer's Disease.Frontiers in pharmacology · 2019Review
- Therapeutic Benefit of Cilostazol in Patients with Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized and Nonrandomized Studies.Journal of vascular and interventional neurology · 2018Article
- Cilostazol ameliorates collagenase-induced cerebral hemorrhage by protecting the blood-brain barrier.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Live Imaging of the Ependymal Cilia in the Lateral Ventricles of the Mouse Brain.Journal of visualized experiments : JoVE · 2015Article
- Three types of ependymal cells with intracellular calcium oscillation are characterized by distinct cilia beating properties.Journal of neuroscience research · 2014Article
- Phenotypic transformation of smooth muscle in vasospasm after aneurysmal subarachnoid hemorrhage.Translational stroke research · 2014Review
- Real-time vascular mechanosensation through ex vivo artery perfusion.Biological procedures online · 2014Article
- Pkd2 mesenteric vessels exhibit a primary defect in endothelium-dependent vasodilatation restored by rosiglitazone.American journal of physiology. Heart and circulatory physiology · 2013Article
- Effects of intravenous human albumin, enteral cilostazol, and combination therapy on the reduction of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage.Frontiers in neurologyArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cilostazol is a phosphodiesterase inhibitor that has been shown to inhibit platelet activation. Endothelin is known to be the most potent endogenous growth promoting and vasoactive peptide. In patients and animal models with stroke, the level of circulating endothelin increases and complicates the recovery progress contributed by vascular constriction (an immediate pathology) and vascular proliferation (a long-term pathology). However, the effects of cilostazol on endothelin have not been explored. To demonstrate the dual-antagonizing effects of cilostazol on vasoconstriction and cell proliferation induced by endothelin, we used primary culture of mouse vascular smooth muscle cells in vitro, mouse femoral artery ex vivo, and intracranial basilar artery ex vivo. We show that the dual-inhibition effects of cilostazol are mediated by blocking endothelin-induced extracellular calcium influx. Although cilostazol does not inhibit endothelin-induced intraorganellar calcium release, blockade of extracellular calcium influx is sufficient to blunt endothelin-induced vasoconstriction. We also show that cilostazol inhibits endothelin-induced cellular proliferation by blocking extracellular calcium influx. Inhibition of cAMP-dependent protein kinase (PKA) can block anti-proliferation activity of cilostazol, confirming the downstream role of PKA in cellular proliferation. To further demonstrate the selectivity of the dual-antagonizing effects of cilostazol, we used a different phosphodiesterase inhibitor. Interestingly, sildenafil inhibits endothelin-induced vasoconstriction but not cellular proliferation in smooth muscle cells. For the first time, we show selective dual-antagonizing effects of cilostazol on endothelin. We propose that cilostazol is an excellent candidate to treat endothelin-associated diseases, such as stroke.
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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.