ArticlePloS one2014
Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Assessing the therapeutic potential of PDE-5 inhibitors in adults: Insights from a multi-omics study.Physiological reports · 2026Article
- High-altitude thrombosis: divergent pathophysiological mechanisms and preventive strategies in acutely exposed population and native highlanders.Frontiers in cardiovascular medicine · 2026Review
- Exploring the Multifaceted Potential of Sildenafil in Medicine.Medicina (Kaunas, Lithuania) · 2023Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Reversal of pulmonary arterial hypertension and neointimal formation by kinin B1 receptor blockade.Respiratory research · 2021Article
- Could Oral Phosphodiesterase 5 Inhibitors Have a Potential Adjuvant Role in Combating COVID-19 Infection?Sexual medicine reviews · 2021Review
- Therapeutic sildenafil inhibits pulmonary damage induced by cigarette smoke exposure and bacterial inhalation in rats.Pharmaceutical biology · 2020Article
- QuantitativeScientific reports · 2020Article
- Inhibitory effects of formononetin on the monocrotaline‑induced pulmonary arterial hypertension in rats.Molecular medicine reports · 2020Article
- Effect of a phosphodiesterase-5A (PDE5A) gene polymorphism on response to sildenafil therapy in canine pulmonary hypertension.Scientific reports · 2019Article
- Relation of Macrophage Migration Inhibitory Factor to Pulmonary Hemodynamics and Vascular Structure and Carbamyl-Phosphate Synthetase I Genetic Variations in Pediatric Patients with Congenital Cardiac Shunts.Mediators of inflammation · 2019Article
- Is p38 MAPK a Dark Force in Right Ventricular Hypertrophy and Failure in Pulmonary Arterial Hypertension?American journal of respiratory cell and molecular biology · 2017Article
- Differences in the renal antifibrotic cGMP/cGKI-dependent signaling of serelaxin, zaprinast, and their combination.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice.Scientific reports · 2017Article
- Article
- Matrix metalloproteinases are possible targets in monocrotaline-induced pulmonary hypertension: investigation of anti-remodeling effects of alagebrium and everolimus.Anatolian journal of cardiology · 2017Article
- Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy.Inflammation · 2016Article
- Sildenafil reduces signs of oxidative stress in pulmonary arterial hypertension: Evaluation by fatty acid composition, level of hydroxynonenal and heart rate variability.Redox biology · 2016Article
- Inflammatory response mechanisms exacerbating hypoxemia in coexistent pulmonary fibrosis and sleep apnea.Mediators of inflammation · 2015Review
- Serum Cytokines in Young Pediatric Patients with Congenital Cardiac Shunts and Altered Pulmonary Hemodynamics.Mediators of inflammationArticle
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pulmonary arterial hypertension (PH) is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT)-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK) phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt) pathway and nuclear factor (NF)-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP)-1, interleukin (IL)-1α, lipopolysaccharide induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.
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