| 1. |
|
|
| 2. |
- Edsfeldt, Andreas, et al.
(författare)
-
Proinflammatory Role of Sphingolipids and Glycosphingolipids in the Human Atherosclerotic Plaque
- 2016
-
Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 36:6, s. 1132-1140
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Lipids are central to the development of atherosclerotic plaques. Specifically, which lipids are culprits remains controversial, and promising targets have failed in clinical studies. Sphingolipids are bioactive lipids present in atherosclerotic plaques, and they have been suggested to have both proatherogenic and antiatherogenic. However, the biological effects of these lipids remain unknown in the human atherosclerotic plaque. The aim of this study was to assess plaque levels of sphingolipids and investigate their potential association with and contribution to plaque vulnerability.APPROACH AND RESULTS: Glucosylceramide, lactosylceramide, ceramide, dihydroceramide, sphingomyelin, and sphingosine-1-phosphate were analyzed in homogenates from 200 human carotid plaques using mass spectrometry. Inflammatory activity was determined by analyzing plaque levels of cytokines and plaque histology. Caspase-3 was analyzed by ELISA technique. Expression of regulatory enzymes was analyzed with RNA sequencing. Human coronary artery smooth muscle cells were used to analyze the potential role of the 6 sphingolipids as inducers of plaque inflammation and cellular apoptosis in vitro. All sphingolipids were increased in plaques associated with symptoms and correlated with inflammatory cytokines. All sphingolipids, except sphingosine-1-phosphate, also correlated with histological markers of plaque instability. Lactosylceramide, ceramide, sphingomyelin, and sphingosine-1-phosphate correlated with caspase-3 activity. In vitro experiments revealed that glucosylceramide, lactosylceramide, and ceramide induced cellular apoptosis. All analyzed sphingolipids induced an inflammatory response in human coronary artery smooth muscle cells.CONCLUSIONS: This study shows for the first time that sphingolipids and particularly glucosylceramide are associated with and are possible inducers of plaque inflammation and instability, pointing to sphingolipid metabolic pathways as possible novel therapeutic targets.
|
|
| 3. |
- Schiopu, A., et al.
(författare)
-
Galectin 3 is a powerful risk predictor for recurrent coronary events in acute coronary syndrome patients
- 2015
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 36:Suppl 1, s. 11-11
-
Konferensbidrag (refereegranskat)abstract
- Background: Galectin 3 and ST2 are mediators and biomarkers of myocardial fibrosis and remodeling that have recently entered the clinical practice guidelines as prognostic factors in heart failure patients. Elevated galectin 3 and ST2 levels in acute myocardial infarction patients have also been associated with increased incidence of adverse events during follow-up. Purpose: We aimed to assess the comparative ability of Galectin 3 and ST2 to offer additional prognostic information for risk stratification in acute coronary syndrome (ACS) patients, on top of traditional cardiovascular risk factors and other established prognostic biomarkers. Methods: We measured the levels of galectin 3, ST2, N-terminal pro-B type natriuretic peptide (NTproBNP), high-sensitivity C-reactive protein (hsCRP), highsensitivity troponin T (TnT), cystatin C, and lipids in plasma collected from 524 ACS patients (STEMI, non-STEMI and unstable angina) on day 1 following the acute event. Biomarker levels were correlated with the risk to develop recurrent coronary events, in linear regression models adjusted for age, sex and traditional risk factors (smoking, diabetes mellitus, hypertension, LDL, HDL and triglycerides). Results: During a mean follow-up period of 2.13 years, 63 (12%) of the patients suffered a new coronary event. Baseline galectin 3, ST2, hsCRP, NTproBNP and cystatin C were significantly higher in these patients compared to the event-free controls. In a Cox proportional hazards model with forward step selection that included all biomarkers alongside traditional risk factors, age (HR per year of age 1.06, 95% CI 1.03-1.09), galectin 3 (HR per SD log increase 1.88, 95% CI 1.41- 2.51) and cystatin C (HR per SD log increase 1.39, 95% CI 1.12-1.74) were selected as the only independent predictors of recurrent events in the population. In receiver operating curve (ROC) analyses, addition of galectin 3 significantly improved the c-statistic of the model based on traditional risk factors alone (0.81 vs. 0.76, P
|
|
| 4. |
- Yndigegn, T., et al.
(författare)
-
Elevated CA125 is associated with incident heart failure and increased mortality in patients with acute coronary syndrome
- 2016
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 37:Suppl 1, s. 1392-1393
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Carbohydrate antigen 125 (CA125) is a mucin produced by serosal cells in response to mechanical and inflammatory stimuli. CA125 has emerged as prognostic biomarker in heart failure (HF) and correlates with markers of fluid overload, echocardiographic parameters and prognosis in HF patients. In patients with acute coronary syndrome (ACS), elevated CA125 is correlated with a higher risk of in-hospital HF. The relationship between CA125 and long-term prognosis in ACS patients has not previously been assessed. Purpose: The purpose of our study was to investigate if CA125 measured at the time of an acute coronary event is related to cardiac remodeling during the first year of follow-up and long-term risk for HF and death Methods: We measured CA125 in plasma within 24 hours of the acute event in 523 patients with acute myocardial infarction or unstable angina admitted to the Coronary Care Unit. Routine echocardiograms were performed in all participants. The primary outcomes were hospitalization with a diagnosis of heart failure or death during follow-up, identified through data from the Swedish Hospital Discharge Register and the Swedish Cause of Death Register. In a subgroup of 109 patients aged 75 years or above we assessed the relationships between baseline CA125 and echocardiographical parameters of cardiac structure and function at 1 year after the index ACS. Results: The median follow-up period was 27.3 months for incident HF and 39.5 months for mortality. In Cox proportional hazards models we found an adjusted hazard ratio of 1.51 (95% CI 1.08-2.12; p
|
|
