Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control study

Abstract Background Subclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in i...

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Main Authors: Marcos Tadashi K. Toyoshima, Monique F. M. Santana, Amanda R. M. Silva, Gabriela B. Mello, Daniele P. Santos-Bezerra, Marisa F. S. Goes, Adriana A. Bosco, Bruno Caramelli, Graziella E. Ronsein, Maria Lucia Correa-Giannella, Marisa Passarelli
Format: Article
Language:English
Published: BMC 2023-03-01
Series:Diabetology & Metabolic Syndrome
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Online Access:https://doi.org/10.1186/s13098-023-01007-y
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author Marcos Tadashi K. Toyoshima
Monique F. M. Santana
Amanda R. M. Silva
Gabriela B. Mello
Daniele P. Santos-Bezerra
Marisa F. S. Goes
Adriana A. Bosco
Bruno Caramelli
Graziella E. Ronsein
Maria Lucia Correa-Giannella
Marisa Passarelli
author_facet Marcos Tadashi K. Toyoshima
Monique F. M. Santana
Amanda R. M. Silva
Gabriela B. Mello
Daniele P. Santos-Bezerra
Marisa F. S. Goes
Adriana A. Bosco
Bruno Caramelli
Graziella E. Ronsein
Maria Lucia Correa-Giannella
Marisa Passarelli
author_sort Marcos Tadashi K. Toyoshima
collection DOAJ
description Abstract Background Subclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality. Methods A total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages. Results Among 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use. Conclusion HDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.
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spelling doaj.art-b360fd97d58248a3a5ac3947aad74ba22023-03-22T11:56:04ZengBMCDiabetology & Metabolic Syndrome1758-59962023-03-0115111410.1186/s13098-023-01007-yProteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control studyMarcos Tadashi K. Toyoshima0Monique F. M. Santana1Amanda R. M. Silva2Gabriela B. Mello3Daniele P. Santos-Bezerra4Marisa F. S. Goes5Adriana A. Bosco6Bruno Caramelli7Graziella E. Ronsein8Maria Lucia Correa-Giannella9Marisa Passarelli10Laboratorio de Lipides (LIM10), Hospital das Clinicas (HCFMUSP) Faculdade de Medicina, Universidade de Sao PauloLaboratorio de Lipides (LIM10), Hospital das Clinicas (HCFMUSP) Faculdade de Medicina, Universidade de Sao PauloDepartamento de Bioquímica, Instituto de Química, Universidade de São PauloLaboratorio de Lipides (LIM10), Hospital das Clinicas (HCFMUSP) Faculdade de Medicina, Universidade de Sao PauloLaboratório de Carboidratos e Radioimunoensaio (LIM18), Hospital das Clinicas (HCFMUSP) Faculdade de Medicina, Universidade de Sao PauloLaboratório de Aterosclerose, Instituto do Coração, Hospital das Clinicas (HCFMUSP) Faculdade de Medicina, Universidade de Sao PauloLaboratório de Carboidratos e Radioimunoensaio (LIM18), Hospital das Clinicas (HCFMUSP) Faculdade de Medicina, Universidade de Sao PauloUnidade de Medicina Interdisciplinar em Cardiologia (UnMic), Instituto do Coração, Hospital das Clinicas (InCor, HCFMUSP) Faculdade de Medicina, Universidade de Sao PauloDepartamento de Bioquímica, Instituto de Química, Universidade de São PauloLaboratório de Carboidratos e Radioimunoensaio (LIM18), Hospital das Clinicas (HCFMUSP) Faculdade de Medicina, Universidade de Sao PauloLaboratorio de Lipides (LIM10), Hospital das Clinicas (HCFMUSP) Faculdade de Medicina, Universidade de Sao PauloAbstract Background Subclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality. Methods A total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages. Results Among 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use. Conclusion HDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.https://doi.org/10.1186/s13098-023-01007-yType 1 diabetes mellitusCardiovascular diseaseHDLProteomicsVascular function
spellingShingle Marcos Tadashi K. Toyoshima
Monique F. M. Santana
Amanda R. M. Silva
Gabriela B. Mello
Daniele P. Santos-Bezerra
Marisa F. S. Goes
Adriana A. Bosco
Bruno Caramelli
Graziella E. Ronsein
Maria Lucia Correa-Giannella
Marisa Passarelli
Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control study
Diabetology & Metabolic Syndrome
Type 1 diabetes mellitus
Cardiovascular disease
HDL
Proteomics
Vascular function
title Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control study
title_full Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control study
title_fullStr Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control study
title_full_unstemmed Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control study
title_short Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control study
title_sort proteomics of high density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus a case control study
topic Type 1 diabetes mellitus
Cardiovascular disease
HDL
Proteomics
Vascular function
url https://doi.org/10.1186/s13098-023-01007-y
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