Significant abnormalities of the HDL phosphosphingolipidome in type 1 diabetes despite normal HDL cholesterol concentration

Denimal, Damien; Barros, Jean‐Paul Pais de; Petit, Jean‐Michel; Bouillet, Benjamin; Vergès, Bruno; Duvillard, Laurence

doi:10.1016/j.atherosclerosis.2015.06.040

Cited by 51 publications

(31 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, the cholesterol extraction capacity of HDLs was not affected by periodontitis, suggesting that only a subset of HDL functions and activities are affected by lowgrade inflammation. Although this study is in line with others (see [5][6][7] for recent publications) that showed disease-induced alterations in HDL functions, its salient point is that low-grade inflammation-associated perturbations in HDL functions and composition could be fully normalized with the resolution of the disease. Hence, HDLs are very plastic particles whose functions are dynamically regulated by transition between healthy and disease states.…”

supporting

confidence: 83%

Genetics and molecular biology

Rütti

Widmann

2015

Current Opinion in Lipidology

View full text Add to dashboard Cite

supporting

confidence: 83%

Genetics and molecular biology

Rütti

Widmann

2015

Current Opinion in Lipidology

View full text Add to dashboard Cite

“…Moreover, it has been reported that the blood S1P levels are maintained within a relatively small range, and minimal changes in S1P levels affect the immune system and human conditions. For instance, it was reported that slight decreases in S1P in high-density lipoprotein of serum was associated with type 1 diabetes mellitus [47]. It is also known that slight decreases in S1P in high density lipoproteins-containing serum fractions is associated with ischemic heart disease [48].…”

Section: Discussionmentioning

confidence: 99%

Breast cancer sphingosine-1-phosphate is associated with phospho-sphingosine kinase 1 and lymphatic metastasis

Tsuchida

Nagahashi

Nakajima

et al. 2016

Journal of Surgical Research

View full text Add to dashboard Cite

Background Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, has been implicated as a key regulatory molecule in cancer through its ability to promote cell proliferation, migration, angiogenesis and lymphangiogenesis. Previous studies suggested that S1P produced by sphingosine kinase 1 (SphK1) in breast cancer plays important roles in progression of disease and metastasis. However, the associations between S1P and clinical parameters in human breast cancer have not been well investigated to date. Materials and Methods We determined levels of S1P and other sphingolipids in breast cancer tissue by electrospray ionization-tandem mass spectrometry. Associations between S1P levels and clinicopathological features of the tumors were analyzed. Expression of phospho-SphK1 (pSphK1) in breast cancer tissues was determined by immunohistochemical scoring. Results Levels of S1P in breast cancer tissues were significantly higher in patients with high white blood cell count in the blood than patients without. S1P levels were lower in patients with HER2 overexpression/amplification than patients without. Further, cancer tissues with high pSphK1 expression showed significantly higher levels of S1P than cancer tissues without. Finally, patients with lymph node metastasis showed significantly higher levels of S1P in tumor tissues than patients with negative nodes. Conclusions To our knowledge, this is the first study to demonstrate that high expression of pSphK1 is associated with higher levels of S1P, which in turn is associated with lymphatic metastasis in breast cancer.

show abstract

“…25,26 However, we could observe no variations in apoM concentrations (Figure VI in the online-only Data Supplement), in accordance with previous reports that apoM is not decreased in non-MODY3 diabetic patients. [27][28][29] An alternative explanation may be defective interaction with cell receptors. Glycation did reduce binding of HDL to cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

Diabetes Mellitus Is Associated With Reduced High-Density Lipoprotein Sphingosine-1-Phosphate Content and Impaired High-Density Lipoprotein Cardiac Cell Protection

Brinck

Thomas

Lauer

et al. 2016

ATVB

View full text Add to dashboard Cite

Objective— The dyslipidemia of type 2 diabetes mellitus has multiple etiologies and impairs lipoprotein functionality, thereby increasing risk for cardiovascular disease. High-density lipoproteins (HDLs) have several beneficial effects, notably protecting the heart from myocardial ischemia. We hypothesized that glycation of HDL could compromise this cardioprotective effect. Approach and Results— We used in vitro (cardiomyocytes) and ex vivo (whole heart) models subjected to oxidative stress together with HDL isolated from diabetic patients and nondiabetic HDL glycated in vitro (methylglyoxal). Diabetic and in vitro glycated HDL were less effective ( P <0.05) than control HDL in protecting from oxidative stress. Protection was significantly, inversely correlated with the degree of in vitro glycation ( P <0.001) and the levels of hemoglobin A1c in diabetic patients ( P <0.007). The ability to activate protective, intracellular survival pathways involving Akt, Stat3, and Erk1/2 was significantly reduced ( P <0.05) using glycated HDL. Glycation reduced the sphingosine-1-phosphate (S1P) content of HDL, whereas the S1P concentrations of diabetic HDL were inversely correlated with hemoglobin A1c ( P <0.005). The S1P contents of in vitro glycated and diabetic HDL were significantly, positively correlated (both <0.01) with cardiomyocyte survival during oxidative stress. Adding S1P to diabetic HDL increased its S1P content and restored its cardioprotective function. Conclusions— Our data demonstrate that glycation can reduce the S1P content of HDL, leading to increased cardiomyocyte cell death because of less effective activation of intracellular survival pathways. It has important implications for the functionality of HDL in diabetes mellitus because HDL-S1P has several beneficial effects on the vasculature.

show abstract

Significant abnormalities of the HDL phosphosphingolipidome in type 1 diabetes despite normal HDL cholesterol concentration

Cited by 51 publications

References 45 publications

Genetics and molecular biology

Genetics and molecular biology

Breast cancer sphingosine-1-phosphate is associated with phospho-sphingosine kinase 1 and lymphatic metastasis

Diabetes Mellitus Is Associated With Reduced High-Density Lipoprotein Sphingosine-1-Phosphate Content and Impaired High-Density Lipoprotein Cardiac Cell Protection

Contact Info

Product

Resources

About