TY - JOUR
T1 - Metabolic signature of arrhythmogenic cardiomyopathy
AU - Volani, Chiara
AU - Rainer, Johannes
AU - Hernandes, Vinicius Veri
AU - Meraviglia, Viviana
AU - Pramstaller, Peter Paul
AU - Smárason, Sigurður Vidir
AU - Pompilio, Giulio
AU - Casella, Michela
AU - Sommariva, Elena
AU - Paglia, Giuseppe
AU - Rossini, Alessandra
N1 - Funding Information:
Funding: This research was supported by the Department of Innovation and Research and University of the Autonomous Province of Bolzano/Bozen, and by the Italian Ministry of Health (RC2019 EF5C ID:2754330).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4
Y1 - 2021/4
N2 - Arrhythmogenic cardiomyopathy (ACM) is a genetic-based cardiac disease accompanied by severe ventricular arrhythmias and a progressive substitution of the myocardium with fibro-fatty tissue. ACM is often associated with sudden cardiac death. Due to the reduced penetrance and variable expressivity, the presence of a genetic defect is not conclusive, thus complicating the diagnosis of ACM. Recent studies on human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) obtained from ACM individuals showed a dysregulated metabolic status, leading to the hypothesis that ACM pathology is characterized by an impairment in the energy metabolism. However, despite efforts having been made for the identification of ACM specific biomarkers, there is still a substantial lack of information regarding the whole metabolomic profile of ACM patients. The aim of the present study was to investigate the metabolic profiles of ACM patients compared to healthy controls (CTRLs). The targeted Biocrates AbsoluteIDQ® p180 assay was used on plasma samples. Our analysis showed that ACM patients have a different metabolome compared to CTRLs, and that the pathways mainly affected include tryptophan metabolism, arginine and proline metabolism and beta oxidation of fatty acids. Altogether, our data indicated that the plasma metabolomes of arrhythmogenic cardiomyopathy patients show signs of endothelium damage and impaired nitric oxide (NO), fat, and energy metabolism.
AB - Arrhythmogenic cardiomyopathy (ACM) is a genetic-based cardiac disease accompanied by severe ventricular arrhythmias and a progressive substitution of the myocardium with fibro-fatty tissue. ACM is often associated with sudden cardiac death. Due to the reduced penetrance and variable expressivity, the presence of a genetic defect is not conclusive, thus complicating the diagnosis of ACM. Recent studies on human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) obtained from ACM individuals showed a dysregulated metabolic status, leading to the hypothesis that ACM pathology is characterized by an impairment in the energy metabolism. However, despite efforts having been made for the identification of ACM specific biomarkers, there is still a substantial lack of information regarding the whole metabolomic profile of ACM patients. The aim of the present study was to investigate the metabolic profiles of ACM patients compared to healthy controls (CTRLs). The targeted Biocrates AbsoluteIDQ® p180 assay was used on plasma samples. Our analysis showed that ACM patients have a different metabolome compared to CTRLs, and that the pathways mainly affected include tryptophan metabolism, arginine and proline metabolism and beta oxidation of fatty acids. Altogether, our data indicated that the plasma metabolomes of arrhythmogenic cardiomyopathy patients show signs of endothelium damage and impaired nitric oxide (NO), fat, and energy metabolism.
KW - ACM
KW - Asymmetric dimethylarginine (ADMA)
KW - Biocrates
KW - Metabolomics
KW - Nitric oxide (NO)
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U2 - 10.3390/metabo11040195
DO - 10.3390/metabo11040195
M3 - Article
AN - SCOPUS:85103905296
SN - 2218-1989
VL - 11
JO - Metabolites
JF - Metabolites
IS - 4
M1 - 195
ER -