scholarly journals Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies

Metabolites ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 621
Author(s):  
Peter McGranaghan ◽  
Jennifer A. Kirwan ◽  
Mariel A. Garcia-Rivera ◽  
Burkert Pieske ◽  
Frank Edelmann ◽  
...  

Lipids represent a valuable target for metabolomic studies since altered lipid metabolism is known to drive the pathological changes in cardiovascular disease (CVD). Metabolomic technologies give us the ability to measure thousands of metabolites providing us with a metabolic fingerprint of individual patients. Metabolomic studies in humans have supported previous findings into the pathomechanisms of CVD, namely atherosclerosis, apoptosis, inflammation, oxidative stress, and insulin resistance. The most widely studied classes of lipid metabolite biomarkers in CVD are phospholipids, sphingolipids/ceramides, glycolipids, cholesterol esters, fatty acids, and acylcarnitines. Technological advancements have enabled novel strategies to discover individual biomarkers or panels that may aid in the diagnosis and prognosis of CVD, with sphingolipids/ceramides as the most promising class of biomarkers thus far. In this review, application of metabolomic profiling for biomarker discovery to aid in the diagnosis and prognosis of CVD as well as metabolic abnormalities in CVD will be discussed with particular emphasis on lipid metabolites.

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2194
Author(s):  
Kamil Łuczykowski ◽  
Natalia Warmuzińska ◽  
Sylwia Operacz ◽  
Iga Stryjak ◽  
Joanna Bogusiewicz ◽  
...  

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.


Author(s):  
Miguel Ruiz‐Canela ◽  
Adela Hruby ◽  
Clary B. Clish ◽  
Liming Liang ◽  
Miguel A. Martínez‐González ◽  
...  

Placenta ◽  
2021 ◽  
Vol 112 ◽  
pp. e33
Author(s):  
Sze Ting (Cecilia) Kwan ◽  
Manjot Virdee ◽  
Nipun Saini ◽  
Kaylee Helfrich ◽  
Susan Smith

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Caterina Oriana Aragona ◽  
Egidio Imbalzano ◽  
Federica Mamone ◽  
Valentina Cairo ◽  
Alberto Lo Gullo ◽  
...  

Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs) in cardiovascular disease, through a systematic review of quantitative studies.Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”.Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included.Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers.Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: ProsperoCRD42015023717.


1991 ◽  
Vol 621 (1 Physiological) ◽  
pp. 277-290 ◽  
Author(s):  
GEORG WICK ◽  
LUKAS A. HUBER ◽  
XU QING-BO ◽  
ELMAR JAROSCH ◽  
DIETHER SCHÖNITZER ◽  
...  

2014 ◽  
Vol 57 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Csilla Tóthová ◽  
Oskar Nagy ◽  
Gabriel Kováč

Abstract. The objective of this study was to determine the concentrations of the main indicators of lipomobilization and selected variables of protein profile in dairy cows after calving, including immunoglobulins and acute phase proteins, as well as to evaluate the relationships between the altered lipid metabolism and changes in protein profile. Into the evaluation we included 54 clinically healthy dairy cows of a Slovak spotted breed, low-land black spotted breed and their crossbreeds in the period of 1-2 weeks after parturition. Blood samples were analysed for non-esterified fatty acids (NEFA, mmol/l), β-hydroxybutyrate (BHB, mmol/l), total proteins (TP, g/l), albumin (Alb, g/l), immunoglobulin G (IgG, g/l), haptoglobin (Hp, g/l) and serum amyloid A (SAA, mg/l). In cows with concentrations of NEFA above 0.35 mmol/l (n=20) we found significantly lower mean serum concentrations of total proteins, albumin and IgG than in cows with serum NEFA concentrations below 0.35 mmol/l (n=34) (P<0.001). On the other hand, cows with higher values of NEFA showed significantly higher mean concentrations of BHB, Hp and SAA (P<0.001). The concentrations of NEFA significantly negatively correlated with the values of TP (P<0.001), albumin (P<0.01) and IgG (P<0.001). Significant positive correlations were found between the concentrations of NEFA and BHB, Hp, as well as SAA (P<0.001). Similar correlations were also found between the values of BHB and the variables of protein profile except for albumin. This study indicates strong relationships between NEFA and selected variables of protein profile in cows after parturition.


1989 ◽  
Vol 49 (4) ◽  
pp. 624-628 ◽  
Author(s):  
A L Olson ◽  
S E Nelson ◽  
C J Rebouche

Gut ◽  
2016 ◽  
Vol 66 (12) ◽  
pp. 2160-2169 ◽  
Author(s):  
Frauke Beilstein ◽  
Matthieu Lemasson ◽  
Véronique Pène ◽  
Dominique Rainteau ◽  
Sylvie Demignot ◽  
...  

ObjectiveHCV is intimately linked with the liver lipid metabolism, devoted to the efflux of triacylglycerols stored in lipid droplets (LDs) in the form of triacylglycerol-rich very-low-density lipoproteins (VLDLs): (i) the most infectious HCV particles are those of lowest density due to association with triacylglycerol-rich lipoproteins and (ii) HCV-infected patients frequently develop hepatic steatosis (increased triacylglycerol storage). The recent identification of lysophosphatidylcholine acyltransferase 1 (LPCAT1) as an LD phospholipid-remodelling enzyme prompted us to investigate its role in liver lipid metabolism and HCV infectious cycle.DesignHuh-7.5.1 cells and primary human hepatocytes (PHHs) were infected with JFH1-HCV. LPCAT1 depletion was achieved by RNA interference. Cells were monitored for LPCAT1 expression, lipid metabolism and HCV production and infectivity. The density of viral particles was assessed by isopycnic ultracentrifugation.ResultsUpon HCV infection, both Huh-7.5.1 cells and PHH had decreased levels of LPCAT1 transcript and protein, consistent with transcriptional downregulation. LPCAT1 depletion in either naive or infected Huh-7.5.1 cells resulted in altered lipid metabolism characterised by LD remodelling, increased triacylglycerol storage and increased secretion of VLDL. In infected Huh-7.5.1 cells or PHH, LPCAT1 depletion increased production of the viral particles of lowest density and highest infectivity.ConclusionsWe have identified LPCAT1 as a modulator of liver lipid metabolism downregulated by HCV, which appears as a viral strategy to increase the triacylglycerol content and hence infectivity of viral particles. Targeting this metabolic pathway may represent an attractive therapeutic approach to reduce both the viral titre and hepatic steatosis.


2017 ◽  
Vol 214 (12) ◽  
pp. 3707-3729 ◽  
Author(s):  
Maria A. Rujano ◽  
Magda Cannata Serio ◽  
Ganna Panasyuk ◽  
Romain Péanne ◽  
Janine Reunert ◽  
...  

The biogenesis of the multi-subunit vacuolar-type H+-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects. The introduction of one of the missense mutations into Drosophila led to reduced survival and altered lipid metabolism. We further demonstrate that in the liver-like fat body, the autophagic dysregulation was associated with defects in lysosomal acidification and mammalian target of rapamycin (mTOR) signaling. Finally, both ATP6AP2 mutations impaired protein stability and the interaction with ATP6AP1, a member of the V0 assembly complex. Collectively, our data suggest that the missense mutations in ATP6AP2 lead to impaired V-ATPase assembly and subsequent defects in glycosylation and autophagy.


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