Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes

<i>Background</i>: Diabetes, particularly type 2 diabetes (T2D), is linked with an increased risk of developing coronary heart disease (CHD). The present study aimed to evaluate potential circulating biomarkers of CHD by adopting a targeted proteomic approach based on proximity extension...

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Main Authors: Giovanni Sartore, Francesco Piarulli, Eugenio Ragazzi, Alice Mallia, Stefania Ghilardi, Massimo Carollo, Annunziata Lapolla, Cristina Banfi
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Proteomes
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Online Access:https://www.mdpi.com/2227-7382/12/4/29
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author Giovanni Sartore
Francesco Piarulli
Eugenio Ragazzi
Alice Mallia
Stefania Ghilardi
Massimo Carollo
Annunziata Lapolla
Cristina Banfi
author_facet Giovanni Sartore
Francesco Piarulli
Eugenio Ragazzi
Alice Mallia
Stefania Ghilardi
Massimo Carollo
Annunziata Lapolla
Cristina Banfi
author_sort Giovanni Sartore
collection DOAJ
description <i>Background</i>: Diabetes, particularly type 2 diabetes (T2D), is linked with an increased risk of developing coronary heart disease (CHD). The present study aimed to evaluate potential circulating biomarkers of CHD by adopting a targeted proteomic approach based on proximity extension assays (PEA). <i>Methods</i>: The study was based on 30 patients with both T2D and CHD (group DC), 30 patients with T2D without CHD (group DN) and 29 patients without diabetes but with a diagnosis of CHD (group NC). Plasma samples were analyzed using PEA, with an Olink Target 96 cardiometabolic panel expressed as normalized protein expression (NPX) units. <i>Results</i>: Lysosomal Pro-X carboxypeptidase (PRCP), Liver carboxylesterase 1 (CES1), Complement C2 (C2), and Intercellular adhesion molecule 3 (ICAM3) were lower in the DC and NC groups compared with the DN groups. Lithostathine-1-alpha (REG1A) and Immunoglobulin lambda constant 2 (IGLC2) were found higher in the DC group compared to DN and NC groups. ROC analysis suggested a significant ability of the six proteins to distinguish among the three groups (whole model test <i>p</i> < 0.0001, AUC 0.83–0.88), with a satisfactory discriminating performance in terms of sensitivity (77–90%) and specificity (70–90%). A possible role of IGLC2, PRCP, and REG1A in indicating kidney impairment was found, with a sensitivity of 92% and specificity of 83%. <i>Conclusions</i>: The identified panel of six plasma proteins, using a targeted proteomic approach, provided evidence that these parameters could be considered in the chronic evolution of T2D and its complications.
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spelling doaj-art-80523643cc374d06b28d918d8cea90fb2024-12-27T14:49:26ZengMDPI AGProteomes2227-73822024-10-011242910.3390/proteomes12040029Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 DiabetesGiovanni Sartore0Francesco Piarulli1Eugenio Ragazzi2Alice Mallia3Stefania Ghilardi4Massimo Carollo5Annunziata Lapolla6Cristina Banfi7Department of Medicine-DIMED, University of Padova, 35122 Padova, ItalyDepartment of Medicine-DIMED, University of Padova, 35122 Padova, ItalyStudium Patavinum, University of Padova, 35122 Padova, ItalyUnit of Functional Proteomics, Metabolomics, and Network Analysis, Centro Cardiologico Monzino IRCCS, 20138 Milan, ItalyUnit of Functional Proteomics, Metabolomics, and Network Analysis, Centro Cardiologico Monzino IRCCS, 20138 Milan, ItalyDepartment of Medicine-DIMED, University of Padova, 35122 Padova, ItalyDepartment of Medicine-DIMED, University of Padova, 35122 Padova, ItalyUnit of Functional Proteomics, Metabolomics, and Network Analysis, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy<i>Background</i>: Diabetes, particularly type 2 diabetes (T2D), is linked with an increased risk of developing coronary heart disease (CHD). The present study aimed to evaluate potential circulating biomarkers of CHD by adopting a targeted proteomic approach based on proximity extension assays (PEA). <i>Methods</i>: The study was based on 30 patients with both T2D and CHD (group DC), 30 patients with T2D without CHD (group DN) and 29 patients without diabetes but with a diagnosis of CHD (group NC). Plasma samples were analyzed using PEA, with an Olink Target 96 cardiometabolic panel expressed as normalized protein expression (NPX) units. <i>Results</i>: Lysosomal Pro-X carboxypeptidase (PRCP), Liver carboxylesterase 1 (CES1), Complement C2 (C2), and Intercellular adhesion molecule 3 (ICAM3) were lower in the DC and NC groups compared with the DN groups. Lithostathine-1-alpha (REG1A) and Immunoglobulin lambda constant 2 (IGLC2) were found higher in the DC group compared to DN and NC groups. ROC analysis suggested a significant ability of the six proteins to distinguish among the three groups (whole model test <i>p</i> < 0.0001, AUC 0.83–0.88), with a satisfactory discriminating performance in terms of sensitivity (77–90%) and specificity (70–90%). A possible role of IGLC2, PRCP, and REG1A in indicating kidney impairment was found, with a sensitivity of 92% and specificity of 83%. <i>Conclusions</i>: The identified panel of six plasma proteins, using a targeted proteomic approach, provided evidence that these parameters could be considered in the chronic evolution of T2D and its complications.https://www.mdpi.com/2227-7382/12/4/29targeted proteomicstype 2 diabetescardiovascular disease
spellingShingle Giovanni Sartore
Francesco Piarulli
Eugenio Ragazzi
Alice Mallia
Stefania Ghilardi
Massimo Carollo
Annunziata Lapolla
Cristina Banfi
Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes
Proteomes
targeted proteomics
type 2 diabetes
cardiovascular disease
title Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes
title_full Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes
title_fullStr Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes
title_full_unstemmed Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes
title_short Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes
title_sort circulating factors as potential biomarkers of cardiovascular damage progression associated with type 2 diabetes
topic targeted proteomics
type 2 diabetes
cardiovascular disease
url https://www.mdpi.com/2227-7382/12/4/29
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