ArticleAging cell2017
Hyperphosphatemia induces senescence in human endothelial cells by increasing endothelin-1 production.
Article in Aging cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Cellular crosstalk between endothelial and vascular smooth muscle cells via the BACH1/COL3A1 axis promotes vascular calcification in chronic kidney disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Metabolic disorders and osteoarthritis: novel insights into pathological mechanisms and therapeutic strategies.Life medicine · 2026Review
- Pathological mechanisms of osteoarthritis in the network of geriatric comorbidities: Emerging insights from organs-crosstalk.Journal of orthopaedic translation · 2026Review
- Pulmonary Vascular Signaling in Pulmonary Hypertension: Potential Role of Endothelial CaArteriosclerosis, thrombosis, and vascular biology · 2026Review
- Association between admission serum phosphate levels and prognosis in post-cardiac arrest patients: a retrospective observational study.BMC cardiovascular disorders · 2026Observational
- Endothelin-1/endothelin B receptor signalling mediates Prx1Journal of orthopaedic translation · 2026Article
- The Exposome and the Kidney: A Silent Dialogue Shaping Chronic Kidney Disease.Journal of xenobiotics · 2025Review
- Aging aggravates cognitive dysfunction in spontaneously hypertensive rats by inducing cerebral microvascular endothelial dysfunction.PloS one · 2025Article
- Renal aging and its consequences: navigating the challenges of an aging population.Frontiers in pharmacology · 2025Review
- Association between Serum Phosphorus Levels and Diabetic Retinopathy: A Cross-Sectional Study.International journal of endocrinology · 2024Article
- Identification and functional analysis of senescent cells in the cardiovascular system using omics approaches.American journal of physiology. Heart and circulatory physiology · 2023Review
- Article
- The Association between Admission Serum Phosphorus and Preoperative Deep Venous Thrombosis in Geriatric Hip Fracture: A Retrospective Study.Diagnostics (Basel, Switzerland) · 2023Article
- Diabetes and Its Cardiovascular Complications: Potential Role of the Acetyltransferase p300.Cells · 2023Review
- Mechanisms and consequences of endothelial cell senescence.Nature reviews. Cardiology · 2023Review
- Endothelin A receptors contribute to senescence of brain microvascular endothelial cells.Canadian journal of physiology and pharmacology · 2022Article
- Cellular senescence: the good, the bad and the unknown.Nature reviews. Nephrology · 2022Review
- Hyperphosphatemia and its relationship with blood pressure, vasoconstriction, and endothelial cell dysfunction in hypertensive hemodialysis patients.BMC nephrology · 2022Observational
- Longitudinal Effects of Serum Calcium and Phosphate Levels and Their Ratio on Incident Ischemic Heart Disease among Korean Adults.Biomolecules · 2022Article
- Phosphate Burden and Organ Dysfunction.Frontiers in aging · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperphosphatemia is related to some pathologies, affecting vascular cell behavior. This work analyzes whether high concentration of extracellular phosphate induces endothelial senescence through up-regulation of endothelin-1 (ET-1), exploring the mechanisms involved. The phosphate donor β-glycerophosphate (BGP) in human endothelial cells increased ET-1 production, endothelin-converting enzyme-1 (ECE-1) protein, and mRNA expression, which depend on the AP-1 activation through ROS production. In parallel, BGP also induced endothelial senescence by increasing p16 expression and the senescence-associated β-galactosidase (SA-ß-GAL) activity. ET-1 itself was able to induce endothelial senescence, increasing p16 expression and SA-ß-GAL activity. In addition, senescence induced by BGP was blocked when different ET-1 system antagonists were used. BGP increased ROS production at short times, and the presence of antioxidants prevented the effect of BGP on AP1 activation, ECE-1 expression, and endothelial senescence. These findings were confirmed in vivo with two animal models in which phosphate serum levels were increased: seven/eight nephrectomized rats as chronic kidney disease models fed on a high phosphate diet and aged mice. Both models showed hyperphosphatemia, higher levels of ET-1, and up-regulation in aortic ECE-1, suggesting a direct relationship between hyperphosphatemia and ET-1. Present results point to a new and relevant role of hyperphosphatemia on the regulation of ET-1 system and senescence induction at endothelial level, both in endothelial cells and aorta from two animal models. The mechanism involved showed a higher ROS production, which probably activates AP-1 transcription factor and, as a result, ECE-1 expression, increasing ET-1 synthesis, which in consequence induces endothelial senescence.
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