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
Source: PubMed


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.

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    • "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. Electronic supplementary material The online version of this article (doi:10.1007/s12263-015-0459-1) contains supplementary material, which is available to authorized users.
    Full-text · Article · May 2015 · Genes & Nutrition
    • "Furthermore, in lean, healthy men, the relative influence of different macronutrients on postprandial adiponectin also remains inconclusive, as adiponectin decreased [9] [12] [17] or increased [7] [16] after the intake of a high-fat (HF) meal, and decreased after carbohydrate intake [12]. Postprandial levels of the gelatinases after dietary intervention in lean, healthy individuals have, conversely, been consistently reported as increased [17] [18] [19] [20] [21]. Although these studies have reported increased blood gelatinase levels after consumption of both HF [17,19–21] and high-carbohydrate [18] meals, none of them examined the differential effect of macronutrients within an isoenergetic context. "
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    ABSTRACT: Objective: Evidence suggests that an acute systemic inflammatory response is invoked after consumption of a high-energy meal. Postprandial regulation of adiponectin, an adipose tissue-derived, anti-inflammatory hormone, and the gelatinases, matrix metalloproteinase (MMP)-2 and MMP-9, endopeptidases implicated in a diverse range of inflammatory processes, remain inconclusive. The aim of this study was to assess the postprandial effect of a high-energy (1212 kcal) meal on plasma adiponectin, MMP-2 and MMP-9 activity, glucose, insulin, triacylglycerols, total cholesterol, high-density lipoprotein cholesterol, and the differential effects on these parameters depending on whether the test meal was high fat (HF; 46 g fat, 1210 kcal) or isoenergetic and low fat (LF; 15 g fat, 1214 kcal energy). Methods: Test meals were consumed by 17 lean, healthy men on two separate occasions with blood samples collected by venipuncture at baseline (0 h) and 1 and 3 h after consumption of each test meal. Results: At baseline, no significant difference was seen in the parameters between the two groups, except for MMP-2, MMP-9, and total cholesterol. Over the 3-h postprandial period, no significant differential effect of the HF versus the LF test meal was observed on adiponectin, MMP-2, MMP-9, or on metabolic markers other than triacylglycerol, which increased significantly in response to the HF test meal (time × treatment, P = 0.002). When analyzed independent of time, MMP-2 (treatment, P = 0.006), MMP-9 (treatment, P = 0.022), and glucose (treatment, P = 0.026) were lower after consumption of the HF meal compared with the LF test meal. When analyzed independent of treatment, adiponectin increased over the 3-h postprandial period (time, P = 0.031), but there was no change in MMP-2 or MMP-9 (time, P = 0.503 and P = 0.525, respectively). Over the 3-h postprandial period, insulin (time, P < 0.001) and total cholesterol (time, P = 0.002) increased, whereas glucose (time, P < 0.001) and high-density lipoprotein cholesterol (time, P < 0.001) decreased. Conclusion: No differential effects of a HF versus a LF isoenergetic meal were seen on postprandial adiponectin or the gelatinases. Adiponectin increased in response to a high-energy meal independent of treatment, and the gelatinases were lower in response to the HF versus the LF isoenergetic meal, independent of time point. Given the considerable amount of time that humans spend in the postprandial state, additional research is necessary to further understand inflammatory changes in this state.
    No preview · Article · Feb 2015 · Nutrition
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    • "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.
    Full-text · Article · Apr 2012 · Metabolomics
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