Lipid Biomarkers for Risk Assessment in Acute Coronary Syndromes

Meeusen, Jeffrey W.; Donato, Leslie J.; Jaffe, Allan S.

doi:10.1007/s11886-017-0863-9

Cited by 15 publications

(10 citation statements)

References 69 publications

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“…specifics, C16:0 and C24:0 ceramides, in both control PXR F=F and huPXR mice. Ceramides are complex sphingolipids that are components of the cell membrane and also play an important role in regulating cellular inflammatory signaling, stress responses, and apoptosis (Meeusen et al 2017(Meeusen et al , 2018Wang et al 2017). Circulating ceramide levels have been independently associated with an increased CVD risk in multiple human studies, and ceramides can also be detected in human atherosclerotic plaques (Bismuth et al 2008;Havulinna et al 2016;Laaksonen et al 2016;Meeusen et al 2018;Uchida et al 2017;Wang et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice

Sui

Meng

Chen

et al. 2021

Environ Health Perspect

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BACKGROUND: Exposure to plastic-associated endocrine disrupting chemicals (EDCs) has been associated with an increased risk of cardiovascular disease (CVD) in humans. However, the underlying mechanisms for this association are unclear. Many EDCs have been shown to function as ligands of the nuclear receptor pregnane X receptor (PXR), which functions as xenobiotic sensor but also has pro-atherogenic effects in vivo. OBJECTIVE: We sought to investigate the contribution of PXR to the adverse effects dicyclohexyl phthalate (DCHP), a widely used phthalate plasticizer, on lipid homeostasis and CVD risk factors. METHODS: Cell-based assays, primary organoid cultures, and PXR conditional knockout and PXR-humanized mouse models were used to investigate the impact of DCHP exposure on PXR activation and lipid homeostasis in vitro and in vivo. Targeted lipidomics were performed to measure circulating ceramides, novel predictors for CVD. RESULTS: DCHP was identified as a potent PXR-selective agonist that led to higher plasma cholesterol levels in wild-type mice. DCHP was then demonstrated to activate intestinal PXR to elicit hyperlipidemia by using tissue-specific PXR-deficient mice. Interestingly, DCHP exposure also led to higher circulating ceramides in a PXR-dependent manner. DCHP-mediated PXR activation stimulated the expression of intestinal genes mediating lipogenesis and ceramide synthesis. Given that PXR exhibits considerable species-specific differences in receptor pharmacology, PXR-humanized mice were also used to replicate these findings. DISCUSSION: Although the adverse health effects of several well-known phthalates have attracted considerable attention, little is known about the potential impact of DCHP on human health. Our studies demonstrate that DCHP activated PXR to induce hypercholesterolemia and ceramide production in mice. These results indicate a potentially important role of PXR in contributing to the deleterious effects of plastic-associated EDCs on cardiovascular health in humans. Testing PXR activation should be considered for risk assessment of phthalates and other EDCs.

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Section: Discussionmentioning

confidence: 99%

Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice

Sui

Meng

Chen

et al. 2021

Environ Health Perspect

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“…Sphingolipids and EV are not only measurable indicator of some biological state or condition in cardiovascular disease, but also causative agents in CAD progression. Growing evidence suggests that the blood levels of ceramides are associated with the exacerbation of myocardial ischemic disease and its complications 7,40,49 . Studies on murine models revealed that pharmacological inhibition of the synthesis of ceramides prevents heart failure after myocardial ischemia, decreasing ventricular remodeling, fibrosis, and inflammatory infiltrate 8,43,50 .…”

Section: Discussionmentioning

confidence: 99%

Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia

Burrello

Biemmi

Dei

et al. 2020

Sci Rep

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Sphingolipids are structural components of cell membrane, displaying several functions in cell signalling. Extracellular vesicles (EV) are lipid bilayer membrane nanoparticle and their lipid composition may be different from parental cells, with a significant enrichment in sphingolipid species, especially in pathological conditions. We aimed at optimizing EV isolation from plasma and describing the differential lipid content of EV, as compared to whole plasma. As pilot study, we evaluated the diagnostic potential of lipidomic signature of circulating EV in patients with a diagnosis of ST-segment-elevation myocardial infarction (STEMI). STEMI patients were evaluated before reperfusion and 24-h after primary percutaneous coronary intervention. Twenty sphingolipid species were quantified by liquid-chromatography tandem-mass-spectrometry. EV-ceramides, -dihydroceramides, and -sphingomyelins increased in STEMI vs. matched controls and decreased after reperfusion. Their levels correlated to hs-troponin, leucocyte count, and ejection fraction. Plasma sphingolipids levels were 500-to-700-fold higher as compared to EV content; nevertheless, only sphingomyelins differed in STEMI vs. control patients. Different sphingolipid species were enriched in EV and their linear combination by machine learning algorithms accurately classified STEMI patients at pre-PCI evaluation. In conclusion, EV lipid signature discriminates STEMI patients. These findings may contribute to the identification of novel biomarkers and signaling mechanisms related to cardiac ischemia.

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“…Previous studies have indicated that distinct ceramide species are closely related to cardiovascular death in patients with coronary heart disease (CHD). Ceramide molecules Cer(d18:1/16:0), which is abbreviated to Cer16:0; Cer(d18:1/18:0), which is abbreviated to Cer18:0; Cer(d18:1/24:1), which is abbreviated to Cer24:1; and their ratios to Cer(d18:1/24:0), which is abbreviated to Cer24:0, have been investigated as new risk stratification factors in patients with CHD (Meeusen et al, 2017;Peterson et al, 2018). In patients with CHD, a high level of Cer16:0, low level of Cer24:0, and a high Cer16:0/Cer24:0 ratio in plasma are related directly to cardiovascular mortality (Tarasov et al, 2014;Laaksonen et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Circulating Ceramide: A New Cardiometabolic Biomarker in Patients With Comorbid Acute Coronary Syndrome and Type 2 Diabetes Mellitus

Cao

Fang

et al. 2020

Front. Physiol.

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This study investigated the association of circulating ceramides in patients with comorbid acute coronary syndrome and type 2 diabetes mellitus (ACS-DM). Methods: A total of 761 patients with coronary heart disease who were admitted to the Department of Cardiology at the Chinese PLA General Hospital from March to August 2018 were enrolled in this study. Of these 761 patients, 282 were diagnosed with acute coronary syndrome (ACS). We selected 65 patients with ACS-DM (ACS-DM group; mean age 64.88 years; 38 men) and 65 patients with ACS but without any comorbidities (ACS group; mean age 64.68 years; 38 men); the two groups were matched by age and sex. We determined four circulating ceramides in 130 plasma samples: Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0). The ceramides in plasma samples from patients with ACS and those from patients with ACS-DM were compared. Pearson correlation coefficients between individual ceramides and traditional cardiovascular risk factors for the whole study population were calculated. Multiple logistic regression models were used to evaluate the relativity between the ceramide and ACS-DM. Results: Compared with the ACS group, the levels of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) and their ratios to Cer(d18:1/24:0) were higher in the ACS-DM group and Cer(d18:1/24:0) was lower in the ACS-DM group (P < 0.05). Correlation analysis demonstrated mild-to-moderate correlations of ceramide and traditional cardiovascular risk factors. There were relatively strong correlations of Cer(d18:1/18:0) and Cer(d18:1/24:1) with C-reactive protein, blood lipids, fasting blood glucose, and glycated hemoglobin A 1 c. In multiple logistic regression models, Cer(d18:1/18:0) [odds ratio (OR) 2.396; 95% confidence interval (CI) 1.103-5.205;

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Lipid Biomarkers for Risk Assessment in Acute Coronary Syndromes

Cited by 15 publications

References 69 publications

Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice

Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice

Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia

Circulating Ceramide: A New Cardiometabolic Biomarker in Patients With Comorbid Acute Coronary Syndrome and Type 2 Diabetes Mellitus

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