ArticleInternational journal of cardiology2014
Increased concentration of circulating angiogenesis and nitric oxide inhibitors induces endothelial to mesenchymal transition and myocardial fibrosis in patients with chronic kidney disease.
Article in International journal of cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Kidney Failure Patients Treated with Dialysis: A Systematic Review and Meta-Analysis.Clinical journal of the American Society of Nephrology : CJASN · 2021Pooled it
- Combination Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (HIDE): A Randomized, Placebo-Controlled, Pilot Trial.Kidney360 · 2020Trial
- Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial.Kidney international · 2019Trial
- Coronary Microvascular Dysfunction in Hemodialysis-Dependent End-Stage Renal Disease: Prevalence, Characteristics, and Prognostic Implications.Circulation reports · 2026Article
- Involvement of Fibulin-5 in endothelial to mesenchymal transition leading to cardiac fibrosis during metabolic syndrome.Journal of translational medicine · 2026Article
- Review
- Chronic Kidney Disease, Circulating Ceramides, and Coronary Microvascular Dysfunction: Insights from the CRUISE-MET Study.Cardiorenal medicine · 2026Observational
- Biofabrication of a 3D human skeletal muscle microenvironment to study the early steps of fibrosis.Materials today. Bio · 2025Article
- Endothelial dysfunction in chronic kidney disease: a clinical perspective.American journal of physiology. Heart and circulatory physiology · 2025Review
- Circulatory endostatin level and risk of cardiovascular events in patients with end-stage renal disease on hemodialysis.Kidney research and clinical practice · 2024Article
- Capillary rarefaction: a missing link in renal and cardiovascular disease?Angiogenesis · 2024Review
- Deletion of the aryl hydrocarbon receptor in endothelial cells improves ischemic angiogenesis in chronic kidney disease.American journal of physiology. Heart and circulatory physiology · 2024Article
- Experimental Models to Study Endothelial to Mesenchymal Transition in Myocardial Fibrosis and Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- The Role of Two Heart Biomarkers in IgA Nephropathy.International journal of molecular sciences · 2023Article
- Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis.Science translational medicine · 2023Article
- Endothelial Cell Dysfunction and Increased Cardiovascular Risk in Patients With Chronic Kidney Disease.Circulation research · 2023Review
- Circulating thrombospondin-2 level for identifying individuals with rapidly declining kidney function trajectory in type 2 diabetes: a prospective study of the Hong Kong West Diabetes Registry.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- Prognostic Impact of Coronary Flow Reserve in Patients With CKD.Kidney international reports · 2023Article
- Obesity accelerates endothelial-to-mesenchymal transition in adipose tissues of mice and humans.Frontiers in cardiovascular medicine · 2023Article
- Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundSudden cardiovascular death is increased in chronic kidney disease (CKD). Experimental CKD models suggest that angiogenesis and nitric oxide (NO) inhibitors induce myocardial fibrosis and microvascular dropout thereby facilitating arrhythmogenesis. We undertook this study to characterize associations of CKD with human myocardial pathology, NO-related circulating angiogenesis inhibitors, and endothelial cell behavior.
methodsWe compared heart (n=54) and serum (n=162) samples from individuals with and without CKD, and assessed effects of serum on human coronary artery endothelial cells (HCAECs) in vitro. Left ventricular fibrosis and capillary density were quantified in post-mortem samples. Endothelial to mesenchymal transition (EndMT) was assessed by immunostaining of post-mortem samples and RNA expression in heart tissue obtained during cardiac surgery. Circulating asymmetric dimethylarginine (ADMA), endostatin (END), angiopoietin-2 (ANG), and thrombospondin-2 (TSP) were measured, and the effect of these factors and of subject serum on proliferation, apoptosis, and EndMT of HCAEC was analyzed.
resultsCardiac fibrosis increased 12% and 77% in stage 3-4 CKD and ESRD and microvascular density decreased 12% and 16% vs. preserved renal function. EndMT-derived fibroblast proportion was 17% higher in stage 3-4 CKD and ESRD (P trend = 0.02). ADMA, ANG, TSP, and END concentrations increased in CKD. Both individual factors and CKD serum increased HCAEC apoptosis (P=0.02), decreased proliferation (P=0.03), and induced EndMT.
conclusionsCKD is associated with an increase in circulating angiogenesis and NO inhibitors, which impact proliferation and apoptosis of cardiac endothelial cells and promote EndMT, leading to cardiac fibrosis and capillary rarefaction. These processes may play key roles in CKD-associated CV disease.
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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.