ArticleJournal of cellular and molecular medicine2008
Sildenafil-mediated neovascularization and protection against myocardial ischaemia reperfusion injury in rats: role of VEGF/angiopoietin-1.
Article in Journal of cellular and molecular medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Selective vulnerability of cerebral vasculature toScience advances · 2026Article
- Treatment with Sildenafil Promotes Angiogenesis and Modulates Immune Response in Ischemic Muscle Tissue.Current issues in molecular biology · 2026Article
- Reinforcement of Transdural Angiogenesis: A Novel Approach to Treating Ischemic Stroke With Cerebral Perfusion Impairment.Journal of stroke · 2025Review
- Exploring the Multifaceted Potential of Sildenafil in Medicine.Medicina (Kaunas, Lithuania) · 2023Review
- Sildenafil, a phosphodiesterase-5 inhibitor, stimulates angiogenesis and bone regeneration in an atrophic non-union model in mice.Journal of translational medicine · 2023Article
- Phosphodiesterase-5 Inhibitors as Therapeutics for Cardiovascular Diseases: A Brief Review.Iranian journal of public health · 2023Review
- Sildenafil reduces bisphosphonate-induced jaw osteonecrosis in rats.Clinical oral investigations · 2023Article
- The efficacy of PDE5 inhibitors in diabetic patients.Andrology · 2023Review
- Sildenafil Citrate Enhances Renal Organogenesis Following Metanephroi Allotransplantation into Non-Immunosuppressed Hosts.Journal of clinical medicine · 2022Article
- Sildenafil-Induced Revascularization of Rat Hindlimb Involves Arteriogenesis through PI3K/AKT and eNOS Activation.International journal of molecular sciences · 2022Article
- Differences in the Expression of KIR, ILT Inhibitory Receptors, and VEGF Production in the Induced Decidual NK Cell Cultures of Fertile and RPL Women.BioMed research international · 2021Article
- The effect of two phosphodiesterase inhibitors on bone healing in mandibular fractures (animal study in rats).Journal of the Korean Association of Oral and Maxillofacial Surgeons · 2020Article
- Therapeutic Angiogenesis of Chinese Herbal Medicines in Ischemic Heart Disease: A Review.Frontiers in pharmacology · 2018Review
- Sildenafil improves blood perfusion in steroid-induced avascular necrosis of femoral head in rabbits via a protein kinase G-dependent mechanism.Acta orthopaedica et traumatologica turcica · 2017Article
- Article
- [Recurrence-free survival after radical prostatectomy and PDE-5 inhibitor intake].Der Urologe. Ausg. A · 2017Article
- Protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats through inhibiting the Cys-C/Wnt signaling pathway.Oncotarget · 2017Article
- Article
- Treatment with Sildenafil and Donepezil Improves Angiogenesis in Experimentally Induced Critical Limb Ischemia.BioMed research international · 2017Article
- Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality.Heart (British Cardiac Society) · 2016Observational
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Sildenafil citrate (SC), a drug for erectile dysfunction, is now emerging as a cardiopulmonary drug. Our study aimed to determine a novel role of sildenafil on cardioprotection through stimulating angiogenesis during ischaemia (I) reperfusion (R) at both capillary and arteriolar levels and to examine the role of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in this mechanistic effect. Rats were divided into: control sham (CS), sildenafil sham (SS), control+IR (CIR) and sildenafil+IR (SIR). Rats were given 0.7 mg/kg, (i.v) of SC or saline 30 min. before occlusion of left anterior descending artery followed by reperfusion (R). Sildenafil treatment increased capillary and arteriolar density followed by increased blood flow (2-fold) compared to control. Treatment with sildenafil demonstrated increased VEGF and Ang-1 mRNA after early reperfusion. PCR data were validated by Western blot analysis. Significant reduction in infarct size, cardiomyocyte and endothelial apoptosis were observed in SC-treated rats. Increased phosphorylation of Akt, eNOS and expression of anti-apoptotic protein Bcl-2, and thioredoxin, hemeoxygenase-1 were observed in SC-treated rats. Echocardiography demonstrated increased fractional shortening and ejection fraction following 45 days of reperfusion in the treatment group. Stress testing with dobutamine infusion and echocardiogram revealed increased contractile reserve in the treatment group. Our study demonstrated for the first time a strong additional therapeutic potential of sildenafil by up-regulating VEGF and Ang-1 system, probably by stimulating a cascade of events leading to neovascularization and conferring myocardial protection in in vivo I/R rat model.
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