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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    • "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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