PMID- 34129696
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20220731
IS  - 1365-2362 (Electronic)
IS  - 0014-2972 (Print)
IS  - 0014-2972 (Linking)
VI  - 51
IP  - 12
DP  - 2021 Dec
TI  - Neutrophil degranulation biomarkers characterize restrictive echocardiographic 
      pattern with diastolic dysfunction in patients with diabetes.
PG  - e13640
LID - 10.1111/eci.13640 [doi]
LID - e13640
AB  - OBJECTIVE: To investigate the potential association between neutrophil 
      degranulation and patterns of myocardial dysfunction in a cohort of patients with 
      type 2 diabetes mellitus (T2DM). BACKGROUND: Two distinct phenotypes of diabetic 
      cardiomyopathy have been described: a restrictive phenotype with diastolic 
      dysfunction (restrictive/DD) and a dilative phenotype with systolic dysfunction 
      (dilative/SD). However, the underlying determinants of these two patterns are not 
      yet recognized. METHODS: In this single-centre, observational, cross-sectional 
      study, 492 patients were recruited. Ultrasonographic measurements were performed 
      by two experienced sonographers, blinded to the clinical data of the 
      participants. Serum biomarkers of neutrophil degranulation were measured by 
      enzyme-linked immunosorbent sandwich assay (ELISA). RESULTS: After adjustment for 
      confounders, resistin, myeloperoxidase, matrix metalloproteinase 8 and matrix 
      metalloproteinase 9/tissue inhibitor of metalloproteinases 1 complex were 
      positively associated with the restrictive/DD pattern compared with the normal 
      pattern. Similarly, MPO was positively associated with the dilative/SD pattern 
      compared with the normal pattern, and resistin was negatively associated with the 
      dilative/SD pattern compared with the restrictive/DD pattern. CONCLUSIONS: 
      Neutrophil degranulation is associated with the restrictive/DD echocardiographic 
      pattern in patients with T2DM, but not with the normal pattern and dilative/SD 
      patterns. Neutrophils could have a pivotal role in the pathogenesis of myocardial 
      dysfunction, and particularly diastolic dysfunction, in patients with T2DM.
CI  - (c) 2021 The Authors. European Journal of Clinical Investigation published by John 
      Wiley & Sons Ltd on behalf of Stichting European Society for Clinical 
      Investigation Journal Foundation.
FAU - Ministrini, Stefano
AU  - Ministrini S
AUID- ORCID: 0000-0003-4358-6411
AD  - Internal Medicine, Angiology and Atherosclerosis, Department of Medicine and 
      Surgery, Universita degli Studi di Perugia, Perugia, Italy.
AD  - Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland.
FAU - Andreozzi, Francesco
AU  - Andreozzi F
AD  - Department of Medical and Surgical Sciences, University 'Magna Graecia' of 
      Catanzaro, Catanzaro, Italy.
FAU - Montecucco, Fabrizio
AU  - Montecucco F
AUID- ORCID: 0000-0003-0823-8729
AD  - Department of Internal Medicine, First Clinic of internal Medicine, University of 
      Genoa, Genoa, Italy.
AD  - IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, 
      Genoa, Italy.
FAU - Minetti, Silvia
AU  - Minetti S
AD  - Internal Medicine, Angiology and Atherosclerosis, Department of Medicine and 
      Surgery, Universita degli Studi di Perugia, Perugia, Italy.
FAU - Bertolotto, Maria
AU  - Bertolotto M
AD  - Internal Medicine, Angiology and Atherosclerosis, Department of Medicine and 
      Surgery, Universita degli Studi di Perugia, Perugia, Italy.
FAU - Liberale, Luca
AU  - Liberale L
AUID- ORCID: 0000-0003-1472-7975
AD  - Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland.
AD  - Department of Internal Medicine, First Clinic of internal Medicine, University of 
      Genoa, Genoa, Italy.
FAU - Mannino, Gaia Chiara
AU  - Mannino GC
AD  - Department of Medical and Surgical Sciences, University 'Magna Graecia' of 
      Catanzaro, Catanzaro, Italy.
FAU - Succurro, Elena
AU  - Succurro E
AD  - Department of Medical and Surgical Sciences, University 'Magna Graecia' of 
      Catanzaro, Catanzaro, Italy.
FAU - Cassano, Velia
AU  - Cassano V
AD  - Department of Medical and Surgical Sciences, University 'Magna Graecia' of 
      Catanzaro, Catanzaro, Italy.
FAU - Miceli, Sofia
AU  - Miceli S
AD  - Department of Medical and Surgical Sciences, University 'Magna Graecia' of 
      Catanzaro, Catanzaro, Italy.
FAU - Perticone, Maria
AU  - Perticone M
AD  - Department of Medical and Surgical Sciences, University 'Magna Graecia' of 
      Catanzaro, Catanzaro, Italy.
FAU - Sesti, Giorgio
AU  - Sesti G
AD  - Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, 
      Italy.
FAU - Sciacqua, Angela
AU  - Sciacqua A
AD  - Department of Medical and Surgical Sciences, University 'Magna Graecia' of 
      Catanzaro, Catanzaro, Italy.
FAU - Carbone, Federico
AU  - Carbone F
AD  - Department of Internal Medicine, First Clinic of internal Medicine, University of 
      Genoa, Genoa, Italy.
AD  - IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, 
      Genoa, Italy.
LA  - eng
GR  - #2754291/Rete Cardiologica of Italian Ministry of Health/
GR  - Fondazione Carige to Prof. F/
PT  - Journal Article
PT  - Observational Study
DEP - 20210624
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (Biomarkers)
RN  - 0 (Resistin)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 3.4.24.34 (Matrix Metalloproteinase 8)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Aged
MH  - Biomarkers/metabolism
MH  - Cardiomyopathy, Dilated/diagnostic imaging/etiology/*metabolism/physiopathology
MH  - Cardiomyopathy, Restrictive/diagnostic 
      imaging/etiology/*metabolism/physiopathology
MH  - Diabetes Mellitus, Type 2/complications/*metabolism/physiopathology
MH  - Diabetic Cardiomyopathies/diagnostic imaging/etiology/*metabolism/physiopathology
MH  - Echocardiography
MH  - Female
MH  - Heart Failure, Diastolic/diagnostic imaging/etiology/metabolism/physiopathology
MH  - Heart Failure, Systolic/diagnostic imaging/etiology/metabolism/physiopathology
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 8/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Middle Aged
MH  - *Neutrophil Activation
MH  - Peroxidase/metabolism
MH  - Resistin/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-1/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/metabolism
PMC - PMC9286613
OTO - NOTNLM
OT  - diabetic cardiomyopathy
OT  - echocardiography
OT  - neutrophils
OT  - resistin
OT  - type 2 diabetes mellitus
COIS- The authors declare they have no conflict of interest.
EDAT- 2021/06/16 06:00
MHDA- 2022/03/17 06:00
PMCR- 2022/07/15
CRDT- 2021/06/15 17:25
PHST- 2021/05/28 00:00 [revised]
PHST- 2021/04/30 00:00 [received]
PHST- 2021/06/11 00:00 [accepted]
PHST- 2021/06/16 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2021/06/15 17:25 [entrez]
PHST- 2022/07/15 00:00 [pmc-release]
AID - ECI13640 [pii]
AID - 10.1111/eci.13640 [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2021 Dec;51(12):e13640. doi: 10.1111/eci.13640. Epub 2021 Jun 
      24.