ArticleEuropean heart journal2022
Vascular dysfunction and increased cardiovascular risk in hypospadias.
Article in European heart journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The potential mechanisms underlying phthalate-induced hypospadias: a systematic review of rodent model studies.Frontiers in endocrinology · 2024Pooled it
- The genetic landscape of hypospadias: clinical insights into inherited and de novo risk factors.Science China. Life sciences · 2026Article
- Genetic Susceptibility and Pathogenesis of Hypospadias.Biochemical genetics · 2026Review
- Vascular Ageing in Conditions Associated with Early-Onset Hypogonadism.Journal of vascular research · 2026Article
- Mortality and Causes of Death in Boys and Men Born With Hypospadias: A Swedish Population-Based Cohort Study.Urology practice · 2025Article
- Vascular Protection of Neferine on Attenuating Angiotensin II-Induced Blood Pressure Elevation by Integrated Network Pharmacology Analysis and RNA-Sequencing Approach.Chinese journal of integrative medicine · 2025Article
- Differences of sex development.Nature reviews. Disease primers · 2025Review
- EndoCompass Project: Research Roadmap for Reproductive and Developmental Endocrinology.Hormone research in paediatrics · 2025Review
- Retrospective studies and quantitative proteomics reveal that abnormal expression of blood pressure, blood lipids, and coagulation related proteins is associated with hypospadias.Human genetics · 2024Article
- Intracavernosal pressure of the erect penis in children with hypospadias.International journal of impotence research · 2024Article
- Effects of Sex Hormones on Vascular Reactivity in Boys With Hypospadias.The Journal of clinical endocrinology and metabolism · 2024Article
- A qualitative content analysis of the experience of living with hypospadias: varying impact on identity and interpersonal relationships.Frontiers in pediatrics · 2024Article
- Risk of Urological Cancer Among Boys and Men Born with Hypospadias: A Swedish Population-based Study.European urology open science · 2023Article
- Whole-exome sequencing study of hypospadias.iScience · 2023Article
- Current perspectives in hypospadias research: A scoping review of articles published in 2021 (Review).Experimental and therapeutic medicine · 2023Article
- Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease.Molecules (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
aimsHypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a surrogate of hypogonadism, we investigated whether hypospadias is associated with vascular dysfunction and is a risk factor for cardiovascular disease. METHODS AND
resultsOur human study spanned molecular mechanistic to epidemiological investigations. Clinical vascular phenotyping was performed in adolescents with hypospadias and controls. Small subcutaneous arteries from penile skin from boys undergoing hypospadias repair and controls were isolated and functional studies were assessed by myography. Vascular smooth muscle cells were used to assess: Rho kinase, reactive oxygen species (ROS), nitric oxide synthase/nitric oxide, and DNA damage. Systemic oxidative stress was assessed in plasma and urine. Hospital episode data compared men with a history of hypospadias vs. controls. In adolescents with hypospadias, systolic blood pressure (P = 0.005), pulse pressure (P = 0.03), and carotid intima-media thickness standard deviation scores (P = 0.01) were increased. Arteries from boys with hypospadias demonstrated increased U46619-induced vasoconstriction (P = 0.009) and reduced acetylcholine-induced endothelium-dependent (P < 0.0001) and sodium nitroprusside-induced endothelium-independent vasorelaxation (P < 0.0001). Men born with hypospadias were at increased risk of arrhythmia [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.4-5.6, P = 0.003]; hypertension (OR 4.2, 95% CI 1.5-11.9, P = 0.04); and heart failure (OR 1.9, 95% CI 1.7-114.3, P = 0.02).
conclusionHypospadias is associated with vascular dysfunction and predisposes to hypertension and cardiovascular disease in adulthood. Underlying mechanisms involve perturbed Rho kinase- and Nox5/ROS-dependent signalling. Our novel findings delineate molecular mechanisms of vascular injury in hypogonadism, and identify hypospadias as a cardiovascular risk factor in males.
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