ArticleJournal of the American Heart Association2022
Sildenafil (Viagra) Aggravates the Development of Experimental Abdominal Aortic Aneurysm.
Article in Journal of the American Heart Association, 2022. 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, 19 citations in OpenAlex.
- Animal Models of Aortic Aneurysm and Dissection: A Comparative Guide for Mechanism, Therapeutic Testing, and Translational Readouts.Biomedicines · 2026Review
- Family-Wide Dysregulation of Phosphodiesterases Alters cAMP/cGMP Microdomains in Thoracic Aortic Aneurysm.Journal of cardiovascular development and disease · 2026Article
- Calcium channel blockers increase the risk of aortic aneurysm and dissection.Nature communications · 2025Article
- β-aminopropionitrile-induced thoracic aortopathy is refractory to cilostazol and sildenafil in mice.PloS one · 2025Article
- Reassessing the role of nitric oxide in the pathogenesis of sphincter of Oddi dysfunction.Gastroenterology report · 2025Review
- miR-30d Attenuates Pulmonary Arterial Hypertension via Targeting MTDH and PDE5A and Modulates the Beneficial Effect of Sildenafil.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- The perspective of cAMP/cGMP signaling and cyclic nucleotide phosphodiesterases in aortic aneurysm and dissection.Vascular pharmacology · 2024Review
- Integrated Bioinformatics Analysis Reveals the Aberrantly Methylated Differentially Expressed Genes in Dilated Cardiomyopathy.International journal of medical sciences · 2024Article
- The Antioxidant/Nitric Oxide-Quenching Agent Cobinamide Prevents Aortic Disease in a Mouse Model of Marfan Syndrome.JACC. Basic to translational science · 2024Article
- Epidemiology, Symptoms and Pathophysiology of Long Covid Complications.Journal of cellular immunology · 2024Article
- Ameliorative effect of hesperidin against high dose sildenafil-induced liver and testicular oxidative stress and altered gene expression in male rats.Laboratory animal research · 2023Article
- Novel pharmacological approaches in abdominal aortic aneurysm.Clinical science (London, England : 1979) · 2023Review
- Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms.Bioactive materials · 2023Article
- Fatal ascending aortic aneurysm in a patient with systemic lupus erythematosus: A case report.Clinical case reports · 2023Article
- A Devastating Tear: Atypical Presentation of Aortic Dissection Discovered on Echocardiography.Cureus · 2023Article
- Risk Factors for Aortic Dissection.US cardiology · 2023Review
- Increased plasma renin by vasodilators promotes the progression of abdominal aortic aneurysm.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Background cGMP-hydrolyzing phosphodiesterase type 5 (PDE5) regulates vascular smooth muscle cell (SMC) contraction by antagonizing cGMP-dependent protein kinase I (PKGI)-dependent SMC relaxation. SMC contractile dysfunction is implicated in the pathogenesis of aortic aneurysm. PDE5 inhibitors have been used for treating erectile dysfunction, such as drug Viagra (sildenafil). However, a few clinical cases have reported the association of Viagra usage with aortic dissection, and reduced PDE5A expression was found in human aortic aneurysm tissues. Therefore, we aimed to investigate the effect of sildenafil on experimental abdominal aortic aneurysm (AAA), the most common form of aortic aneurysm in elderly men. Methods and Results AAA was induced in C57BL/6J male mice by periaortic elastase in combination with blocking elastin/collagen formation via 3-aminopropionitrile fumarate salt for 35 days. PDE5A protein levels detected by immunostaining were significantly reduced in mouse AAA. Sildenafil application in drinking water significantly aggravated aortic wall dilation and elastin degradation with pre-existing moderate AAA. The phosphorylation level of myosin light chain 2 at Ser19, a biochemical marker of SMC contraction, was significantly reduced by sildenafil in AAA. Proximity ligation assay further revealed that the interaction between cGMP and PKGI was significantly increased by sildenafil in AAA, suggesting an elevation of PKGI activation in AAA. Conclusions Sildenafil treatment aggravated the degradation of elastin fibers and progression of experimental AAA by dysregulating cGMP and contractile signaling in SMCs. Our findings may raise the caution of clinical usage of Viagra in aneurysmal patients.
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