ArticleThe Journal of clinical investigation2022
Targeting the ASMase/S1P pathway protects from sortilin-evoked vascular damage in hypertension.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026Review
- Lysolecithin reprogramming via LPCAT1 modulation restores endothelial function and prevents diabetes-associated dysmetabolism.Cardiovascular diabetology · 2026Article
- Blood-borne sphingosine 1-phosphate maintains vascular resistance, blood pressure, and cardiac function in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The role of sortilin in cardiovascular calcification: mechanisms and therapeutic potential.Frontiers in cardiovascular medicine · 2026Review
- Mitochondrial accumulation of GRK2 as a protective mechanism against hypoxia-induced endothelial dysfunction.Cell death discovery · 2025Article
- Acid sphingomyelinase promotes diabetic cardiomyopathy via disruption of mitochondrial calcium homeostasis.Cardiovascular diabetology · 2025Article
- Emerging roles of the acid sphingomyelinase/ceramide pathway in metabolic and cardiovascular diseases: Mechanistic insights and therapeutic implications.World journal of cardiology · 2025Review
- Plasma miR-1-3p levels predict severity in hospitalized COVID-19 patients.British journal of pharmacology · 2025Article
- Sphingolipid Metabolism and Signalling Pathways in Heart Failure: From Molecular Mechanism to Therapeutic Potential.Journal of inflammation research · 2025Review
- Zonation and ligand and dose dependence of sphingosine 1-phosphate receptor-1 signalling in blood and lymphatic vasculature.Cardiovascular research · 2024Article
- Evaluating SORT1 and SESN1 genes expression in peripheral blood mononuclear cells and oxidative stress status in patients with coronary artery disease.BMC genomic data · 2024Article
- Ying and Yang of Ceramide in the Vascular Endothelium.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Ceramides as Emerging Players in Cardiovascular Disease: Focus on Their Pathogenetic Effects and Regulation by Diet.Advances in nutrition (Bethesda, Md.) · 2024Review
- The Acid Sphingomyelinase Inhibitor Amitriptyline Ameliorates TNF-α-Induced Endothelial Dysfunction.Cardiovascular drugs and therapy · 2024Article
- Molecular Mechanisms Underlying Vascular Remodeling in Hypertension.Reviews in cardiovascular medicine · 2024Review
- C2CD4B Evokes Oxidative Stress and Vascular Dysfunction via a PI3K/Akt/PKCα-Signaling Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone ofJournal of Zhejiang University. Science. B · 2023Article
- Enhanced selective capture of phosphomonoester lipids enabling highly sensitive detection of sphingosine 1-phosphate.Analytical and bioanalytical chemistry · 2023Article
- Interventions to Address Cardiovascular Risk in Obese Patients: Many Hands Make Light Work.Journal of cardiovascular development and disease · 2023Review
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
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Authors and funding
27 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sortilin has been positively correlated with vascular disorders in humans. No study has yet evaluated the possible direct effect of sortilin on vascular function. We used pharmacological and genetic approaches coupled with study of murine and human samples to unravel the mechanisms recruited by sortilin in the vascular system. Sortilin induced endothelial dysfunction of mesenteric arteries through NADPH oxidase 2 (NOX2) isoform activation, dysfunction that was prevented by knockdown of acid sphingomyelinase (ASMase) or sphingosine kinase 1. In vivo, recombinant sortilin administration induced arterial hypertension in WT mice. In contrast, genetic deletion of sphingosine-1-phosphate receptor 3 (S1P3) and gp91phox/NOX2 resulted in preservation of endothelial function and blood pressure homeostasis after 14 days of systemic sortilin administration. Translating these research findings into the clinical setting, we detected elevated sortilin levels in hypertensive patients with endothelial dysfunction. Furthermore, in a population-based cohort of 270 subjects, we showed increased plasma ASMase activity and increased plasma levels of sortilin, S1P, and soluble NOX2-derived peptide (sNOX2-dp) in hypertensive subjects, and the increase was more pronounced in hypertensive subjects with uncontrolled blood pressure. Our studies reveal what we believe is a previously unrecognized role of sortilin in the impairment of vascular function and in blood pressure homeostasis and suggest the potential of sortilin and its mediators as biomarkers for the prediction of vascular dysfunction and high blood pressure.
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