PMID- 38245742
OWN - NLM
STAT- MEDLINE
DCOM- 20240122
LR  - 20240313
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 23
IP  - 1
DP  - 2024 Jan 20
TI  - Multiplexed MRM-based proteomics for identification of circulating proteins as 
      biomarkers of cardiovascular damage progression associated with diabetes 
      mellitus.
PG  - 36
LID - 10.1186/s12933-024-02125-1 [doi]
LID - 36
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of coronary heart 
      disease (CHD) by 2-4 fold, and is associated with endothelial dysfunction, 
      dyslipidaemia, insulin resistance, and chronic hyperglycaemia. The aim of this 
      investigation was to assess, by a multimarker mass spectrometry approach, the 
      predictive role of circulating proteins as biomarkers of cardiovascular damage 
      progression associated with diabetes mellitus. METHODS: The study considered 34 
      patients with both T2DM and CHD, 31 patients with T2DM and without CHD, and 30 
      patients without diabetes with a diagnosis of CHD. Plasma samples of subjects 
      were analysed through a multiplexed targeted liquid chromatography mass 
      spectrometry (LC-MS)-based assay, namely Multiple Reaction Monitoring (MRM), 
      allowing the simultaneous detection of peptides derived from a protein of 
      interest. Gene Ontology (GO) Analysis was employed to identify enriched GO terms 
      in the biological process, molecular function, or cellular component categories. 
      Non-parametric multivariate methods were used to classify samples from patients 
      and evaluate the relevance of the analysed proteins' panel. RESULTS: A total of 
      81 proteins were successfully quantified in the human plasma samples. Gene 
      Ontology analysis assessed terms related to blood microparticles, extracellular 
      exosomes and collagen-containing extracellular matrix. Preliminary evaluation 
      using analysis of variance (ANOVA) of the differences in the proteomic profile 
      among patient groups identified 13 out of the 81 proteins as significantly 
      different. Multivariate analysis, including cluster analysis and principal 
      component analysis, identified relevant grouping of the 13 proteins. The first 
      main cluster comprises apolipoprotein C-III, apolipoprotein C-II, apolipoprotein 
      A-IV, retinol-binding protein 4, lysozyme C and cystatin-C; the second one 
      includes, albeit with sub-grouping, alpha 2 macroglobulin, afamin, kininogen 1, 
      vitronectin, vitamin K-dependent protein S, complement factor B and 
      mannan-binding lectin serine protease 2. Receiver operating characteristic (ROC) 
      curves obtained with the 13 selected proteins using a nominal logistic regression 
      indicated a significant overall distinction (p < 0.001) among the three groups of 
      subjects, with area under the ROC curve (AUC) ranging 0.91-0.97, and sensitivity 
      and specificity ranging from 85 to 100%. CONCLUSIONS: Targeted mass spectrometry 
      approach indicated 13 multiple circulating proteins as possible biomarkers of 
      cardiovascular damage progression associated with T2DM, with excellent 
      classification results in terms of sensitivity and specificity.
CI  - (c) 2024. The Author(s).
FAU - Piarulli, Francesco
AU  - Piarulli F
AD  - Department of Medicine - DIMED, University of Padova, Padova, Italy.
FAU - Banfi, Cristina
AU  - Banfi C
AD  - Centro Cardiologico Monzino, IRCCS, Milano, 20138, Italy. cristina.banfi@ccfm.it.
FAU - Ragazzi, Eugenio
AU  - Ragazzi E
AD  - Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 
      Padova, Italy. eugenio.ragazzi@unipd.it.
FAU - Gianazza, Erica
AU  - Gianazza E
AD  - Centro Cardiologico Monzino, IRCCS, Milano, 20138, Italy.
FAU - Munno, Marco
AU  - Munno M
AD  - Centro Cardiologico Monzino, IRCCS, Milano, 20138, Italy.
FAU - Carollo, Massimo
AU  - Carollo M
AD  - Department of Medicine - DIMED, University of Padova, Padova, Italy.
FAU - Traldi, Pietro
AU  - Traldi P
AD  - Istituto di Ricerca Pediatrica Citta della Speranza, Padova, Italy.
FAU - Lapolla, Annunziata
AU  - Lapolla A
AD  - Department of Medicine - DIMED, University of Padova, Padova, Italy.
FAU - Sartore, Giovanni
AU  - Sartore G
AD  - Department of Medicine - DIMED, University of Padova, Padova, Italy.
LA  - eng
PT  - Journal Article
DEP - 20240120
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Biomarkers)
RN  - 0 (Peptides)
RN  - 0 (Blood Proteins)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 2/diagnosis
MH  - Proteomics/methods
MH  - Biomarkers
MH  - Peptides
MH  - Blood Proteins
PMC - PMC10800045
OTO - NOTNLM
OT  - Blood proteins
OT  - Cardiovascular disease
OT  - Diabetes mellitus
OT  - Gene Ontology analysis
OT  - Mass spectrometry
OT  - Multiple reaction monitoring
OT  - Proteomics
COIS- The authors declare no competing interests.
EDAT- 2024/01/21 00:42
MHDA- 2024/01/22 06:42
PMCR- 2024/01/20
CRDT- 2024/01/20 23:28
PHST- 2023/05/12 00:00 [received]
PHST- 2024/01/07 00:00 [accepted]
PHST- 2024/01/22 06:42 [medline]
PHST- 2024/01/21 00:42 [pubmed]
PHST- 2024/01/20 23:28 [entrez]
PHST- 2024/01/20 00:00 [pmc-release]
AID - 10.1186/s12933-024-02125-1 [pii]
AID - 2125 [pii]
AID - 10.1186/s12933-024-02125-1 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2024 Jan 20;23(1):36. doi: 10.1186/s12933-024-02125-1.