Lipidomic and metabolomic analyses reveal potential plasma biomarkers of early atheromatous plaque formation in hamsters

Jové, Mariona; Ayala, Victòria; Ramírez‐Núñez, Omar; Serrano, José; Cassanyé, Anna; Arola, Lluı́s; Caimari, Antoni; Bas, Josep Maria del; Crescenti, Anna; Pamplona, Reinald; Portero‐Otín, Manuel

doi:10.1093/cvr/cvs368

Cited by 63 publications

(49 citation statements)

References 56 publications

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“…Increased TSH mRNA levels and circulating TSH were significantly associated with reduced markers of cellular senescence (including BAX, DBC1, TP53, TNF gene expression [12,13] and specific glucosylceramides [21,23]) and increased telomere length in both human and rat AT. These data agree with the positive association between serum TSH levels and longevity reported in rodents [1][2][3] and euthyroid humans [3][4][5][6][7][8][9].…”

Section: Discussionmentioning

confidence: 97%

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Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

Moreno-Navarrete

Liñares-Pose

Sabater

et al. 2018

Cell Physiol Biochem

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Background/Aims: Thyroid hormones have been recently linked to senescence and longevity. Given the recent description of TSHB mRNA in human adipose tissue (AT), we aimed to investigate the relationship between local AT TSH and adipose tissue senescence. Methods: TSHB mRNA (measured by real-time PCR) and markers of adipose tissue senescence [BAX, DBC1, TP53, TNF (real-time PCR), telomere length (Telo TAGGG Telomere Length Assay) and lipidomics (liquid chromatography mass spectrometry)] were analysed in subcutaneous (SAT) and visceral (VAT) AT from euthyroid subjects. The chronic effects of TSH were also investigated in AT from hypothyroid rats and after recombinant human TSH (rhTSH) administration in human adipocytes. Results: Both VAT and SAT TSHB gene expression negatively correlated with markers of AT cellular senescence (BAX, DBC1, TP53, TNF gene expression and specific glucosylceramides) and positively associated with telomere length. Supporting these observations, both rhTSH administration in human adipocytes and increased TSH in hypothyroid rats resulted in decreased markers of cellular senescence (Bax and Tp53 mRNA) in both gonadal and subcutaneous white adipose tissue. Conclusion: These data point to a possible role of TSH in AT cellular senescence.

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Section: Discussionmentioning

confidence: 97%

“…The capillary voltage was 3500 V with a scan rate of 1 scan/s. Targeted lipidomic approach was chosen to detect the abundance of specific senescence-associated glucosylceramides [21].…”

Section: Lipidomic Analysesmentioning

confidence: 99%

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

Moreno-Navarrete

Liñares-Pose

Sabater

et al. 2018

Cell Physiol Biochem

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“…Two ml of chloroform (containing 13 C cholesterol as internal standard) were added to 1 ml of cell lysate and vortexed for 10 s. Then, 0.75 ml of KCl 0.7% were added and vortexed for 10 s. The samples were centrifuged at 1000 g during 15 min at 4 °C and chloroform phase (lower) was separated in a glass tube, evaporated using a Speed Vac (Thermo Fisher Scientific, Barcelona, Spain) and resuspended in 200 μl of methanol/chloroform (3:1)56. For LC-Q-TOF-based lipid molecular species analyses, lipid extracts were subjected to liquid chromatography-mass-spectrometry using a HPLC 1290 series coupled to ESI-Q-TOF MS/MS 6520 (Agilent Technologies, Barcelona, Spain).…”

Section: Methodsmentioning

confidence: 99%

7-dehydrocholesterol efficiently supports Ret signaling in a mouse model of Smith-Opitz-Lemli syndrome

Gou-Fàbregas

Macià

Anerillas

et al. 2016

Sci Rep

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Smith-Lemli-Opitz syndrome (SLOS) is a rare disorder of cholesterol synthesis. Affected individuals exhibit growth failure, intellectual disability and a broad spectrum of developmental malformations. Among them, renal agenesis or hypoplasia, decreased innervation of the gut, and ptosis are consistent with impaired Ret signaling. Ret is a receptor tyrosine kinase that achieves full activity when recruited to lipid rafts. Mice mutant for Ret are born with no kidneys and enteric neurons, and display sympathetic nervous system defects causing ptosis. Since cholesterol is a critical component of lipid rafts, here we tested the hypothesis of whether the cause of the above malformations found in SLOS is defective Ret signaling owing to improper lipid raft composition or function. No defects consistent with decreased Ret signaling were found in newborn Dhcr7−/− mice, or in Dhcr7−/− mice lacking one copy of Ret. Although kidneys from Dhcr7−/− mice showed a mild branching defect in vitro, GDNF was able to support survival and downstream signaling of sympathetic neurons. Consistently, GFRα1 correctly partitioned to lipid rafts in brain tissue. Finally, replacement experiments demonstrated that 7-DHC efficiently supports Ret signaling in vitro. Taken together, our findings do not support a role of Ret signaling in the pathogenesis of SLOS.

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“…Free cholesterol in the aorta was positively correlated with taurocholic acid, suggesting that it could be a biomarker for early atherogenesis (30). Furthermore, a high fat cholesterol choate (HFCC) diet has been shown to alter plasma and urinary metabolism in LDLreceptor deficient mice using H-NMR spectroscopy.…”

Section: Atherosclerosismentioning

confidence: 99%

Metabolomics in atherosclerosis

Djekic

Nicoll

Novo

et al. 2015

IJC Metabolic & Endocrine

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It is well established that atherosclerotic cardiovascular disease (ACD) is a leading cause of death in the West. There are several predisposing factors for ACD, which can be divided into two groups: firstly modifiable risk factors, including hypertension, dyslipidaemia, type 2 diabetes mellitus, obesity, smoking and a sedentary lifestyle and secondly the unmodifiable risk factors such as age, gender and heredity. Since single biomarkers are unable to provide sufficient information about the biochemical pathways responsible for the disease, there is a need for a holistic approach technology, e.g. metabolomics, that provide sufficiently detailed information about the metabolic status and assay results will be able to guide food, drug and lifestyle optimisation. Rather than investigating a single pathway, metabolomics deal with the integrated identification of biological and pathological molecular pathways. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are the two most commonly used techniques for metabolite profiling. This detailed review concluded that metabolomics investigations seem to have great potential in identifying small groups of disturbed metabolites which if put together should draw various metabolic routs that lead to the common track pathophysiology. The current evidence in using metabolomics in atherosclerotic cardiovascular disease is also limited and morewell designed studies remain to be established, which might significantly improve the comprehension of atherosclerosis pathophysiology and consequently management.

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Lipidomic and metabolomic analyses reveal potential plasma biomarkers of early atheromatous plaque formation in hamsters

Abstract: The use of comparative liquid chromatography/mass spectrometry-based lipidomics and metabolomics allows the discovery of novel pathways in atherogenesis, as well as new potential plasma biomarkers, which could allow us to predict disease in its early stages and measure its progression.

Cited by 63 publications

References 56 publications

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

7-dehydrocholesterol efficiently supports Ret signaling in a mouse model of Smith-Opitz-Lemli syndrome

Metabolomics in atherosclerosis

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