FABP3 as Biomarker of Heart Pathology

Catalucci, Daniele; Latronico, Michael V.G.; Condorelli, Gianluigi

doi:10.1007/978-94-007-7696-8_22

Cited by 5 publications

(4 citation statements)

References 68 publications

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“…This could be because some of these markers as previously discussed may be associated with more severe and acute injury, which were not present in our military sample, and therefore were not significantly elevated in our cohorts. Further, plasma levels of these protein biomarkers were within the range of control levels reported by others (Missler et al, 1998;Song et al, 2011;Catalucci et al, 2015).…”

Section: Discussionsupporting

confidence: 80%

Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

et al. 2020

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The differential diagnosis between mild Traumatic Brain Injury (mTBI) sequelae and Post-Traumatic Stress Disorder (PTSD) is challenging due to their symptomatic overlap and co-morbidity. As such, there is a need to develop biomarkers which can help with differential diagnosis of these two conditions. Studies from our group and others suggest that blood and brain lipids are chronically altered in both mTBI and PTSD. Therefore, examining blood lipids presents a minimally invasive and cost-effective approach to identify promising biomarkers of these conditions. Using liquid chromatography-mass spectrometry (LC-MS) we examined hundreds of lipid species in the blood of healthy active duty soldiers (n = 52) and soldiers with mTBI (n = 21), PTSD (n = 34) as well as co-morbid mTBI and PTSD (n = 13) to test whether lipid levels were differentially altered with each. We also examined if the apolipoprotein E (APOE) ε4 allele can affect the association between diagnosis and peripheral lipid levels in this cohort. We show that several lipid classes are altered with diagnosis and that there is an interaction between diagnosis and the ε4 carrier status on these lipids. Indeed, total lipid levels as well as both the degree of unsaturation and chain lengths are differentially altered with diagnosis and ε4 status, specifically long chain unsaturated triglycerides (TG) and both saturated and mono-unsaturated diglycerides (DG). Additionally, an examination of lipid species reveals distinct profiles in each diagnostic group stratified by ε4 status, mainly in TG, saturated DG species and polyunsaturated phosphatidylserines. In summary, we show that peripheral lipids are promising biomarker candidates to assist with the differential diagnosis of mTBI and PTSD. Further, ε4 carrier status alone and in interaction with diagnosis has a strong influence on peripheral lipid levels. Therefore, examining ε4 status along with peripheral lipid levels could help with differential diagnosis of mTBI and PTSD.

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Section: Discussionsupporting

confidence: 80%

Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

et al. 2020

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“…MB was expected to be a dominant species in the heart cytosolic proteome, since it is a cytoplasmic hemoprotein which is highly expressed in cardiomyocytes . FABP3 is also highly abundant in the cytoplasm of cardiomyocytes, playing an important role in fatty acid metabolism, and has been proposed as an early biomarker of myocardial injury. − CRYAB is an important chaperone protein which is responsible for binding misfolded proteins in the cytoplasm and also appeared to be highly abundant in the cytosolic protein mixture . The other larger metabolic enzymes which are present in the LM (on the basis of gel visualization) were undetected in the LM mass spectrum due to signal suppression by the lower-MW protein species.…”

Section: Resultsmentioning

confidence: 99%

“…We analyzed fraction 8 collected from sSEC fractionation of pig heart tissue extract and isolated intermediate size (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) proteins for top-down analysis ( Figure 4A). For MDH and CKM, we selected the highest abundance ions with the highest charge (34+ and 44+, respectively), since ECD fragmentation is more efficient for higher-charged protein ions.…”

Section: Sequence Characterization Of Metabolic Enzymesmentioning

confidence: 99%

A Top-Down Proteomics Platform Coupling Serial Size Exclusion Chromatography and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

et al. 2019

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Mass spectrometry (MS)-based top-down proteomics provides rich information about proteoforms arising from combinatorial amino acid sequence variations and post-translational modifications (PTMs). Fourier transform ion cyclotron resonance (FT-ICR) MS affords ultra-high resolving power and provides high-accuracy mass measurements, presenting a powerful tool for top-down MS characterization of proteoforms. However, detection and characterization of large proteins from complex mixtures remain challenging due to the exponential decrease in S:N with increasing molecular weight (MW) and co-eluting low-MW proteins; thus, size-based fractionation of complex protein mixtures prior to MS analysis is necessary. Here, we directly combine MScompatible serial size exclusion chromatography (sSEC) fractionation with 12 T FT-ICR MS for targeted top-down characterization of proteins from complex mixtures extracted from the human and swine heart proteome. Benefiting from the ultra-high resolving power of FT-ICR, we isotopically resolved 31 distinct proteoforms (30-50 kDa) simultaneously in a single mass spectrum within a 100 m/z window. Notably, within a 5 m/z window, we obtained baseline isotopic resolution for 6 distinct large proteoforms (30-50 kDa). The ultra-high resolving power of FT-ICR MS combined with sSEC fractionation enabled targeted top-down analysis of large proteoforms (>30 kDa) from the human heart proteome without extensive chromatographic separation or protein purification. Further separation of proteoforms inside of the mass spectrometer (in-MS) allowed for isolation of individual proteoforms for targeted electron capture dissociation (ECD) for high sequence coverage. sSEC/FT-ICR ECD facilitated identification and sequence characterization of important metabolic enzymes. This platform, which facilitates deep *

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“…FABP3 encodes a fatty acid transporter of long-chain fatty acids and is related to the PPAR/RXR signaling pathway. FABP3 participates in lipid β-oxidation and has been linked to cardiovascular risk ( Jordal et al., 2006 , De Lange et al., 2008 , Zhang et al., 2013 , Thumser et al., 2014 , Catalucci et al., 2015 ). However, FABP3 is associated with carcass back fat thickness and intramuscular fat content in the pig, suggesting that FABP3 is also involved in fat metabolism ( Cho et al., 2011 , Diaz et al., 2015 , Shimada et al., 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Ovary removal modifies liver message RNA profiles in single Comb White Leghorn chickens

Bao

et al. 2020

Poultry Science

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Ovaries produce sex hormones, and ovariectomized animals are often used as models for ovarian dysfunction. The liver is a vital organ involved in metabolism and immunity. In the present study, we conducted experiments to investigate the effects of ovariectomy on transcription and metabolic processes in the liver in chicken. Eight Single Comb White Leghorn (SCWL) female chickens were ovariectomized at 17 wk of age, and 8 intact SCWL females served as controls. At 100 wk of age, all chickens were euthanized. High-throughput transcriptome sequencing was performed on liver RNA obtained from ovariectomized and intact females. A total of 267 differentially expressed genes (DEG) were identified in our study. After analysis using DAVID functional annotation tool, one significant Kyoto Encyclopedia of Genes and Genomes pathway, the phosphatidylinositol signaling pathway, was clustered. Gene Ontology enrichment analysis yielded 46 significant Gene Ontology terms. Among terms describing biological processes, the glycerolipid metabolic and lipid localization processes were dominant. The anabolic genes, PEPCK and GK5 , and the catabolic genes, VTG1 ; VTG2 ; PLD5 ; DGKQ ; DGKE ; and FABP3, were detected in ovariectomized chickens. Differentially expressed genes such as ENSGALG00000000162 , IL-1Β , SVOPL, and CA12 implied that livers in ovariectomized chickens were subjected to strong inflammatory reactions, whereas defenses against endogenous materials were compromised. A comprehensive view of gene expression in the liver of ovariectomized chickens would advance our understanding of lipid metabolism, glycometabolism, and their relationships to pathologies induced by absence of the ovary. The identified DEG indicated that ovariectomy disturbed lipid metabolism in the liver and was accompanied by an increase in hepatic gluconeogenesis and reductions in phosphatidic acid synthesis and lipid carrier capacity.

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FABP3 as Biomarker of Heart Pathology

Cited by 5 publications

References 68 publications

Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

A Top-Down Proteomics Platform Coupling Serial Size Exclusion Chromatography and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

Ovary removal modifies liver message RNA profiles in single Comb White Leghorn chickens

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