title: Diabetes Mellitus Is Associated With Reduced High-Density Lipoprotein Sphingosine-1-Phosphate Content and Impaired High-Density Lipoprotein Cardiac Cell Protection.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.). jonas.brinck@ki.se.
authors.forename: Jonas W
authors.initials: JW
authors.lastname: Brinck
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Aurélien
authors.initials: A
authors.lastname: Thomas
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Estelle
authors.initials: E
authors.lastname: Lauer
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: François R
authors.initials: FR
authors.lastname: Jornayvaz
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Brulhart-Meynet
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Prost
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Pataky
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Patrik
authors.initials: P
authors.lastname: Löfgren
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Johan
authors.initials: J
authors.lastname: Hoffstedt
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Mats
authors.initials: M
authors.lastname: Eriksson
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Camilla
authors.initials: C
authors.lastname: Pramfalk
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Sandrine
authors.initials: S
authors.lastname: Morel
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Kwak
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Miranda
authors.initials: M
authors.lastname: van Eck
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Richard W
authors.initials: RW
authors.lastname: James
authors.affiliation: From the Department of Internal Medicine, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Medical Faculty, Geneva University, Geneva, Switzerland (J.W.B., F.R.J., M.-C.B.-M., R.W.J., M.A.F.); University Centre of Legal Medicine, Unit of Toxicology, Lausanne-Geneva, Switzerland (A.T., E.L., J.-C.P.); Faculty of Biology and Medicine, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland (A.T.); Department of Community Medicine, Service of Therapeutic Education for Chronic Diseases, WHO Collaborating Centre, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland (Z.P.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (J.W.B., P.L., J.H., M.E.); Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden (C.P.); Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden (C.P.); Department of Pathology and Immunology, Medical Faculty, Geneva University, Geneva, Switzerland (S.M., B.R.K.); and Leiden Academic Centre for Drug Research, Division of Biopharmaceutics, Cluster of BioTherapeutics, Leiden University, Leiden, The Netherlands (M.v.E.).
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Frias
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016022:Case-Control Studies; D002470:Cell Survival; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D058065:Diabetic Cardiomyopathies / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D050171:Dyslipidemias / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D000067268:Isolated Heart Preparation; D008075:Lipoproteins, HDL / Q000097:blood*; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010641:Phenotype; D034622:RNA Interference; D017208:Rats, Wistar; D051122:Scavenger Receptors, Class B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D013997:Time Factors; D014162:Transfection
chemical_list: D006442:Glycated Hemoglobin; D008075:Lipoproteins, HDL; D008246:Lysophospholipids; D051122:Scavenger Receptors, Class B; D013110:Sphingosine; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; C517652:hemoglobin A1c protein, human; C060506:sphingosine 1-phosphate
keywords: AGE; HDL; cardiomyocytes; glycation; ischemia reperfusion injury; sphingosine-1-phosphate; type 2 diabetes mellitus