ArticleCardiovascular diabetology2014
The compensatory enrichment of sphingosine -1- phosphate harbored on glycated high-density lipoprotein restores endothelial protective function in type 2 diabetes mellitus.
Article in Cardiovascular diabetology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Treatment with the herbal medicine, naoxintong improves the protective effect of high-density lipoproteins on endothelial function in patients with type 2 diabetes.Molecular medicine reports · 2016Trial
- The regulation of COX-2, ABCA1, and ABCG1 by the lncRNA PACERR links the inflammatory response and cholesterol homeostasis.Cell reports · 2026Article
- HDL metabolism and function in diabetes mellitus.Nature reviews. Endocrinology · 2026Review
- The compensatory enrichment of sphingosine-1-phosphate on HDL in FSGS enhances the protective function of glomerular endothelial cells compared to MCD.Scientific reports · 2025Article
- Emerging Roles for Sphingolipids in Cardiometabolic Disease: A Rational Therapeutic Target?Nutrients · 2024Review
- Common mechanisms underlying diabetic vascular complications: focus on the interaction of metabolic disorders, immuno-inflammation, and endothelial dysfunction.Cell communication and signaling : CCS · 2023Review
- Signal Transduction and Gene Regulation in the Endothelium.Cold Spring Harbor perspectives in medicine · 2023Review
- Review
- Sphingosine 1-phosphate Stimulates Insulin Secretion and Improves Cell Survival by Blocking Voltage-dependent KFrontiers in pharmacology · 2021Article
- Ozanimod to Treat Relapsing Forms of Multiple Sclerosis: A Comprehensive Review of Disease, Drug Efficacy and Side Effects.Neurology international · 2020Review
- Sphingosine 1-Phosphate in Malaria Pathogenesis and Its Implication in Therapeutic Opportunities.Frontiers in cellular and infection microbiology · 2020Review
- Novel Insights into the Role of HDL-Associated Sphingosine-1-Phosphate in Cardiometabolic Diseases.International journal of molecular sciences · 2019Review
- Sphingosine 1-phosphate and inflammation.International immunology · 2019Review
- The Role of High-Density Lipoproteins in Diabetes and Its Vascular Complications.International journal of molecular sciences · 2018Review
- Vascular protection by high-density lipoprotein-associated sphingosine-1-phosphate.Journal of geriatric cardiology : JGC · 2017Review
- Angiopoietin-Like Protein 4 Is a High-Density Lipoprotein (HDL) Component for HDL Metabolism and Function in Nondiabetic Participants and Type-2 Diabetic Patients.Journal of the American Heart Association · 2017Article
- The pleiotropic vasoprotective functions of high density lipoproteins (HDL).Journal of biomedical research · 2017Article
- The role of sphingolipid signalling in diabetes‑associated pathologies (Review).International journal of molecular medicine · 2017Review
- Vascular endothelial dysfunction and pharmacological treatment.World journal of cardiology · 2015Review
- HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.Frontiers in pharmacology · 2015Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundGlycation of high-density lipoprotein (HDL) decreases its ability to induce cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release in endothelial cells. Whether lipid content of HDL, especially sphingosine-1-phosphate (S1P), plays any specific role in restoring the protective function of HDL in type 2 diabetes mellitus (T2DM) is still unknown. METHODS AND
resultsImmunochemical techniques demonstrated that glycated HDL loses its protective function of regulating COX-2 expression compared with diabetic HDL. We proved that the lipid content, especially phospholipid content differed between diabetic HDL and glycated HDL. Levels of HDL-c-bound S1P were increased in T2DM compared with control subjects as detected by UPLC-MS/MS (HDL-c-bound S1P in control subjects vs. T2DM: 309.1 ± 13.71 pmol/mg vs. 382.1 ± 24.45 pmol/mg, P < 0.05). Additionally, mRNA levels of S1P lyase enzymes and S1P phosphatase 1/2 were decreased in peripheral blood by real-time PCR. Antagonist of S1P receptor 1 and 3 (S1PR1/3) diminished the functional difference between apoHDL&PL (HDL containing the protein components and phospholipids) and diabetic apoHDL&PL (diabetic HDL containing the protein components and phospholipids). With different doses of S1P reconstituted on glycated HDL, its function in inducing the COX-2 expression was restored to the same level as diabetic HDL. The mechanism of S1P reconstituted HDL (rHDL) in the process of regulating COX-2 expression involved the phosphorylation of ERK/MAPK-CREB signal pathway. CONCLUSION/SIGNIFICANCE: S1P harbored on HDL is the main factor which restores its protective function in endothelial cells in T2DM. S1P and its receptors are potential therapeutic targets in ameliorating the vascular dysfunction in T2DM.
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