Postprandial serum induces apoptosis in endothelial cells: Role of polymorphonuclear-derived myeloperoxidase and metalloproteinase-9 activity
Research Center of Cardiovascular Biology, Division of Cardiology, Department of Internal Medicine, University of Genova, Italy. Atherosclerosis
(Impact Factor: 3.99).
07/2008; 198(2):458-67. DOI: 10.1016/j.atherosclerosis.2007.11.030
Postprandial state is a pro-inflammatory condition associated with a transient impairment of endothelial function. Recent evidence suggests that myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9) are involved in the pathogenesis of inflammatory vascular diseases such as atherosclerosis. The present study was carried out to investigate whether a fat meal induces polymorphonuclear (PMN) activation and increases the plasma activity of MPO and MMP-9 and whether postprandial serum exerts pro-apoptotic effects on endothelial cells. Fifteen healthy young men underwent a high-fat challenge containing 60g butter. Blood samples were drawn before, and 1, 2, and 4h after the meal. Leukocyte reactive oxygen species (ROS) production, plasma MPO and MMP-9 activity, endothelial-derived soluble CD146 levels, and advanced oxidation protein product (AOPP) levels were determined. Human umbilical vein endothelial cells (HUVECs) were treated with human sera to evaluate mitochondrial membrane potential, ROS production, annexin PI staining, and caspase-3 activity. Triglycerides, ROS production, MPO activity, AOPP levels, pro-MMP-9 zymographic activity, and soluble CD146 levels significantly increased during the 4h after the test meal. Postprandial serum significantly decreased the mitochondrial membrane potential, and increased the rate of ROS production, the percentage of annexin-positive HUVECs, and caspase-3 activity. A strong relationship was observed between postprandial increase in PMN-derived MPO and pro-MMP-9 activity, and the increased rate of apoptosis of endothelial cells exposed to postprandial serum. Data show that postprandial serum exerts pro-apoptotic effects on endothelial cells. The close relationships between markers of endothelial cell apoptosis and MPO and pro-MMP-9 activity suggest that the latter may contribute to the development of fat meal induced endothelial damage.
Available from: Suzan Wopereis
- "addition of glucose and protein in OPGLTT augments the endothelial response . Accordingly , postprandial levels of myeloperoxidase ( MPO ) , and matrix metallopeptidases ( MMP ) - 1 and MMP - 9 , which have been linked to impaired endothelial function , were increased by OPGLTT or a mixed meal challenge ( Cheng et al . 2010 ; Pellis et al . 2012 ; Spallarossa et al . 2008 ) . Many studies report that OPGLTT induces temporary increase in numbers of leukocytes ( Cheng et al . 2010 ; Coutinho et al . 2008 ; MacEneaney et al . 2009 ; van Oos - trom et al . 2003 , 2004 ; Tamburrelli et al . 2012 ; Wopereis et al . 2013 ) . The increase in leukocyte numbers is primarily due to increased neutrophil numbers . Th"
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ABSTRACT: Nutrition research is struggling to demonstrate beneficial health effects, since nutritional effects are often subtle and long term. Health has been redefined as the ability of our body to cope with daily-life challenges. Physiology acts as a well-orchestrated machinery to adapt to the continuously changing environment. We term this adaptive capacity "phenotypic flexibility." The phenotypic flexibility concept implies that health can be measured by the ability to adapt to conditions of temporary stress, such as physical exercise, infections or mental stress, in a healthy manner. This may offer a more sensitive way to assess changes in health status of healthy subjects. Here, we performed a systematic review of 61 studies applying different nutritional stress tests to quantify health and nutritional health effects, with the objective to define an optimal nutritional stress test that has the potential to be adopted as the golden standard in nutrition research. To acknowledge the multi-target role of nutrition, a relevant subset of 50 processes that govern optimal health, with high relevance to diet, was used to define phenotypic flexibility. Subsequently, we assessed the response of biomarkers related to this subset of processes to the different challenge tests. Based on the obtained insights, we propose a nutritional stress test composed of a high-fat, high-caloric drink, containing 60 g palm olein, 75 g glucose and 20 g dairy protein in a total volume of 400 ml. The use of such a standardized nutritional challenge test in intervention studies is expected to demonstrate subtle improvements of phenotypic flexibility, thereby enabling substantiation of nutritional health effects.
Genes & Nutrition 05/2015; 10(3):459. DOI:10.1007/s12263-015-0459-1 · 2.79 Impact Factor
Available from: Suzan Wopereis
- "In our current study, this was reflected by increased plasma levels of myeloperoxidase (MPO) and matrix metallopeptidase 9 (MMP9) (cluster 5) and by decreased levels of the antioxidant uric acid (cluster 4). Postprandial increase of MPO and MMP9 was also observed by Spallarossa et al. (Spallarossa et al. 2008). It was suggested that these two enzymes contribute to impaired endothelial function in response to intake of a fat meal. "
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ABSTRACT: We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify the postprandial response of multiple metabolic processes in humans in a standardized manner. The PCT comprised consumption of a standardized 500 ml dairy shake containing respectively 59, 30 and 12 energy percent lipids, carbohydrates and protein. During a 6 h time course after PCT 145 plasma metabolites, 79 proteins and 7 clinical chemistry parameters were quantified. Multiple processes related to metabolism, oxidation and inflammation reacted to the PCT, as demonstrated by changes of 106 metabolites, 31 proteins and 5 clinical chemistry parameters. The PCT was applied in a dietary intervention study to evaluate if the PCT would reveal additional metabolic changes compared to non-perturbed conditions. The study consisted of a 5-week intervention with a supplement mix of anti-inflammatory compounds in a crossover design with 36 overweight subjects. Of the 231 quantified parameters, 31 had different responses over time between treated and control groups, revealing differences in amino acid metabolism, oxidative stress, inflammation and endocrine metabolism. The results showed that the acute, short term metabolic responses to the PCT were different in subjects on the supplement mix compared to the controls. The PCT provided additional metabolic changes related to the dietary intervention not observed in non-perturbed conditions. Thus, a metabolomics based quantification of a standardized perturbation of metabolic homeostasis is more informative on metabolic status and subtle health effects induced by (dietary) interventions than quantification of the homeostatic situation.
Electronic supplementary material
The online version of this article (doi:10.1007/s11306-011-0320-5) contains supplementary material, which is available to authorized users.
Metabolomics 04/2012; 8(2):347-359. DOI:10.1007/s11306-011-0320-5 · 3.86 Impact Factor
Available from: ncbi.nlm.nih.gov
- "The plasma obtained from humans is unavoidably quite variable; yet we were surprised to see highly conserved expression of adhesion molecules in the endothelial cells incubated with the preexposure plasma samples. We derived several details for the assay design from a recent study that found postprandial conditions to be stressful to endothelial cells (Spallarossa et al., 2008); therefore, we suspect that the strict control of the exposure protocol was essential to our being able to ascertain the ICAM-1 and VCAM-1 increases. The format of the assay allowed us to compare both the time frame of adhesion molecule mRNA induction as well as consider a dose response to the plasma; both factors affected the expression. "
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ABSTRACT: The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen dioxide (NO(2)). Plasma samples were obtained from human volunteers exposed to 100 μg/m(3) DE or filtered air for 2 h. A second cohort was exposed to 500 ppb NO(2) or filtered air in an identical protocol. Primary human coronary artery endothelial cells (hCAECs) were grown to confluence and treated for 24 h with a 10 or 30% (in media) mixture of plasma obtained before, immediately post or 24 h postexposure to pollutant exposures. Messenger RNA (mRNA) was isolated from hCAECs following the incubation and probed for intracellular cell adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) expression. ICAM-1 mRNA expression was increased by plasma obtained at both timepoints following the NO(2) exposures. VCAM-1 was significantly elevated in cells treated with plasma obtained 24 h following diesel exposure and at both timepoints following NO(2) exposure. Interleukin-8 protein was elevated in the hCAEC supernatant when cells were incubated with plasma from NO(2) exposures. These data indicate that proinflammatory circulating factors are elevated acutely following exposure to both DE and a primary component thereof, NO(2). These functional translational assays offer novel approaches to assessing the cardiovascular risk associated with air pollution exposure.
Toxicological Sciences 02/2012; 127(1):179-86. DOI:10.1093/toxsci/kfs084 · 3.85 Impact Factor
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