Detection of Ceramide, a Risk Factor for Coronary Artery Disease, in Human Coronary Plaques by Fluorescent Angioscopy

Uchida, Yasumi; Uchida, Yukiko; Kobayashi, T; Shirai, Seiichiro; Hiruta, Nobuyuki; Shimoyama, Ei; Tabata, Tsuyoshi

doi:10.1253/circj.cj-17-0363

Cited by 16 publications

(12 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the phenotypic heterogeneity of MIs may dilute somewhat the prognostic performance of ceramides, although some authors argue that these lipids can provide more specific information to particular MI categories ( 13 ). Interestingly, two independent imaging studies have confirmed the localization and association of ceramides with the thin fibrotic plaques with necrotic core, supporting further the assumption that ceramides play an important role in plaque vulnerability in atherosclerotic CAD and thus may associate with fatal complications related to rupture prone inflammatory plaques ( 25 , 26 ).…”

Section: Ceramides In Cardiovascular Diseasesmentioning

confidence: 52%

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

et al. 2020

View full text Add to dashboard Cite

Ceramides are bioactive lipids that have an important role in many cellular functions such as apoptosis and inflammation. During the past decade emerging clinical data have shown that ceramides are not only of great biochemical interest but may also have diagnostic utility. Ceramides have shown independent predictive value for negative cardiovascular outcomes as well as for the onset of type 2 diabetes. Based on abundant published data, risk score using the concentrations of circulating ceramides have been developed and adapted for routine clinical practice. Currently serum ceramides are used clinically as efficient risk stratifiers for primary and secondary prevention of atherosclerotic cardiovascular disease (CVD). A direct cause-effect relationship between CVD and ceramide has not been established to date. As ceramide-specific medications are being developed, conventional strategies such as lipid lowering agents and lifestyle interventions can be used to reduce overall risk. Ceramides can identify a very high-risk coronary heart disease category of patients in need for more intense medical attention, specifically those patients at higher risk as highlighted in the 2019 European Society of Cardiology guidelines for stable chronic coronary syndrome patients. In addition, the ceramide risk score may be used as a decision-making tool in primary prevention patients with moderate CVD risk. Finally, the ceramide risk score may have a unique utility as a motivational tool to increase patient's adherence to medical therapy and lifestyle changes.

show abstract

Section: Ceramides In Cardiovascular Diseasesmentioning

confidence: 52%

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

et al. 2020

View full text Add to dashboard Cite

show abstract

“…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). For example, both C16:0 and C24:0 ceramides have been associated with the risk of major adverse cardiovascular events, including death, independent of other risk factors, such as LDL levels, in humans (Bismuth et al 2008;Havulinna et al 2016;Meeusen et al 2018;Wang et al 2017;Zhao et al 2019).…”

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

View full text Add to dashboard Cite

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.

show abstract

“…This is consistently and specifically reported in the ceramide species with an acyl chain length of 18 carbons (CerC18:0). Plasma levels of CerC18:0 are elevated in coronary plaques, a hallmark of CAD pathophysiology [ 11 ]. Evidence from numerous studies also implicates CerC18:0 in the biochemical profile of various neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Ceramide Accumulation Is Associated with Declining Verbal Memory in Coronary Artery Disease Patients: An Observational Study

Chan

Saleem

Herrmann

et al. 2018

JAD

View full text Add to dashboard Cite

Background:Biomarkers in cognitively vulnerable populations, like those with coronary artery disease (CAD), may inform earlier intervention in vascular neurodegeneration. Circulating ceramide C18:0 (CerC18:0) is associated with changes in verbal memory in early neurodegeneration and CAD progression.Objective:To investigate whether plasma CerC18:0 accumulation is associated with longitudinal declines in verbal memory performance in CAD.Methods:In addition to total CerC18:0, we assessed its relative abundance to its precursors as ratios: CerC18:0 to monohexosylceramide C18:0 (MHxCer18:0), CerC18:0 to sphingomyelin C18:0 (SM18:0), and CerC18:0 to sphingosine-1-phosphate (S1P). Verbal memory was assessed using the California Verbal Learning Test 2nd Ed. Using mixed models in 60 CAD participants, we evaluated associations between baseline CerC18:0 ratios and changes in verbal memory performance, adjusting for age, body mass index, and education. Given that cognitive decline is more rapid following onset of deficits, these associations were compared between those with possible mild vascular neurocognitive disorder (MVND).Results:Increased baseline CerC18:0 concentrations correlated with worse verbal memory performance over time (b[SE] = – 0.91[0.30], p = 0.003). Increased baseline CerC18:0/SM18:0 (b[SE] = – 1.11[`], p = 0.03) were associated with worse verbal memory performance over time. These associations were not mediated by whether or not patients had possible MVND at baseline.Conclusion:These findings support aberrant CerC18:0 metabolism as an early neurobiological change in vascular neurodegeneration. Future studies should measure enzymes responsible for conversion of sphingolipid precursors into CerC18:0 to assess enzymatic activity.

show abstract

Detection of Ceramide, a Risk Factor for Coronary Artery Disease, in Human Coronary Plaques by Fluorescent Angioscopy

Cited by 16 publications

References 19 publications

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

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

Ceramide Accumulation Is Associated with Declining Verbal Memory in Coronary Artery Disease Patients: An Observational Study

Contact Info

Product

Resources

About