Lipidomics, Atrial Conduction, and Body Mass Index

M, Fabiola Del Greco; Foco, Luisa; Teumer, Alexander; Verweij, Niek; Paglia, Giuseppe; Meraviglia, Viviana; Melotti, Roberto; Vuković, Vladimir; Rauhe, Werner; Joshi, Peter K.; Demirkan, Ayşe; Felix, Stephan B.; Pietzner, Maik; Said, M. Abdullah; Vegte, Yordi J. van de; Harst, Pim van der; Wright, Alan F.; Hicks, Andrew A.; Campbell, Harry; Dörr, Marcus; Snieder, Harold; Wilson, James F.; Pramstaller, Peter P.; Rossini, Alessandra; Pattaro, Cristian

doi:10.1161/circgen.118.002384

Cited by 9 publications

(4 citation statements)

References 39 publications

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“…This result is consistent with previous data reporting altered lipid metabolites and, in particular, a minor amount of lysoPC a C20:3 in AF patients [ 11 ]. Moreover, in a recent analysis [ 48 ] conducted in a related population-based study from the same region, we observed an association between higher levels of another phosphatydilcholine, the PC38:3, and longer P wave duration, which is also a risk factor for AF [ 49 ]. Even though the association was replicated in an independent population sample from Scotland, proving its robustness, mediation and Mendelian randomization analyses showed that the association between PC38:3 and P wave was caused by the confounding role of BMI: in fact, BMI was proven to cause both PC38:3 increase and P wave prolongation [ 48 ].…”

Section: Discussionmentioning

confidence: 96%

Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study

et al. 2021

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Atrial fibrillation (AF) is a supraventricular arrhythmia deriving from uncoordinated electrical activation with considerable associated morbidity and mortality. To expand the limited understanding of AF biological mechanisms, we performed two screenings, investigating the genetic and metabolic determinants of AF in the Cooperative Health Research in South Tyrol study. We found 110 AF cases out of 10,509 general population individuals. A genome-wide association scan (GWAS) identified two novel loci (p-value < 5 × 10−8) around SNPs rs745582874, next to gene PBX1, and rs768476991, within gene PCCA, with genotype calling confirmed by Sanger sequencing. Risk alleles at both SNPs were enriched in a family detected through familial aggregation analysis of the phenotype, and both rare alleles co-segregated with AF. The metabolic screening of 175 metabolites, in a subset of individuals, revealed a 41% lower concentration of lysophosphatidylcholine lysoPC a C20:3 in AF cases compared to controls (p-adj = 0.005). The genetic findings, combined with previous evidence, indicate that the two identified GWAS loci may be considered novel genetic rare determinants for AF. Considering additionally the association of lysoPC a C20:3 with AF by metabolic screening, our results demonstrate the valuable contribution of the combined genomic and metabolomic approach in studying AF in large-scale population studies.

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Section: Discussionmentioning

confidence: 96%

Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study

et al. 2021

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“…In addition, the minimal volume of the sample collected onto VAMS enables longitudinal metabolomic studies and is particularly in line with the 3R’s principle [ 14 ]. The integration of VAMS with conventional mass spectrometry (MS)-based metabolomics approaches is an attractive solution for different applications, ranging from animal studies to human population studies [ 27 , 28 ] and longitudinal studies [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

VAMS-Based Blood Capillary Sampling for Mass Spectrometry-Based Human Metabolomics Studies

Volani

Malfertheiner²,

Caprioli³

et al. 2023

Metabolites

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Volumetric absorptive microsampling (VAMS) is a recently developed sample collection method that enables single-drop blood collection in a minimally invasive manner. Blood biomolecules can then be extracted and processed for analysis using several analytical platforms. The integration of VAMS with conventional mass spectrometry (MS)-based metabolomics approaches is an attractive solution for human studies representing a less-invasive procedure compared to phlebotomy with the additional potential for remote sample collection. However, as we recently demonstrated, VAMS samples require long-term storage at −80 °C. This study investigated the stability of VAMS samples during short-term storage and compared the metabolome obtained from capillary blood collected from the fingertip to those of plasma and venous blood from 22 healthy volunteers. Our results suggest that the blood metabolome collected by VAMS samples is stable at room temperature only for up to 6 h requiring subsequent storage at −80 °C to avoid significant changes in the metabolome. We also demonstrated that capillary blood provides better coverage of the metabolome compared to plasma enabling the analysis of several intracellular metabolites presented in red blood cells. Finally, this work demonstrates that with the appropriate pre-analytical protocol capillary blood can be successfully used for untargeted metabolomics studies.

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“…Techniques of lipidomics have been applied in some clinical studies for assessing the association of AF. One study found that BMI-correlated increased PC 38:3 was associated with atrial conduction, which was represented by P wave duration 61 . Another study found that AF patients had different fatty acids and phospholipids in the plasma than healthy controls 62 .…”

Section: Discussionmentioning

confidence: 99%

Association of lipid composition and unsaturated fatty acids of VLDL with atrial remodeling in metabolic syndrome

Lee

Cheng

Lung

et al. 2023

Sci Rep

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Subjects with metabolic syndrome (MetS) commonly have atrial remodeling, which indicates a risk for atrial fibrillation. This study determined MetS-related changes in lipid components in very-low-density lipoprotein (VLDL), which has been shown to cause atrial remodeling, the effect of statins on these changes, and the correlation between atrial remodeling and VLDL lipid compositions. Blood samples were collected from 12 non-MetS and 27 sex- and age-matched MetS subjects. Fourteen patients with MetS (MetS-off statin) discontinued statin therapy 14 days before the study, while the remaining 13 remained on it (MetS-on statin). The VLDLs were isolated and processed for mass-based lipid profiling. Lipidomic analyses were performed and associated with atrial remodeling markers measured using standard echocardiography and electrocardiography. Compared with the VLDL components of the non-MetS group, glucosyl/galactosyl ceramide, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were enriched in the MetS-off statin group. Statin therapy attenuated all abnormally abundant lipid classes in MetS, except for triglycerides. In addition, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were significantly correlated with atrial dilatation, and the latter two were also correlated with the PR interval. Enrichment of double bonds, which indicate unsaturated fatty acids, was also significantly correlated with atrial remodeling and P-wave duration. This study suggests that the pathological lipid payload of MetS-VLDL may contribute to atrial remodeling in patients.

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Lipidomics, Atrial Conduction, and Body Mass Index

Cited by 9 publications

References 39 publications

Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study

Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study

VAMS-Based Blood Capillary Sampling for Mass Spectrometry-Based Human Metabolomics Studies

Association of lipid composition and unsaturated fatty acids of VLDL with atrial remodeling in metabolic syndrome

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