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Abstract: In renal disease, elevated levels of urea lead to an increased concentration of cyanate that reacts irreversible with amino groups of proteins through carbamylation reactions. High concentrations of carbamylated low-density-lipoproteins (cLDL) have recently been reported to accumulate in plasma of pateints with chronic renal failure, indicating that cLDL is by far the most abundant modified LDL found in human plasa. Of importance, carbamylated proteins may also be formed directly at sites of inflammation - even in the absence of renal disease- via the phagocyte derived inflammatory mediator myeloperoxidase (MPO). Active MPO is present in human atherosclerotic lesion material and has been shown to bind to low- and high-density lipoproteins. Thus, it can be assumed that MPO derived cyanate contributes to lipoprotein carbamylation at sites of inflammation. Recent clinical studies demonstrated that carbamylated proteins predict increased risk of coronary artery disease, future myocardial infarction, stroke and death.

No endothelial receptors of binding proteins that might trigger the potent pro-atherosclerotic effects of carbamylated LDL have yet been identified. Therefore, the aim of the proposed project is to identify endothelial receptors for carbamylated LDL and to systemically examine the impact of carbamylated LDL on the expression of inflammatory genes in human derived vascular endothelial cells.

Keywords: pathophysiology; medical biochemistry; Vascular biology; pharmacology

Funded by: FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria

Project results published: > Aging affects high-density lipoprotein composition... Biochim Biophys Acta. 2013; 1831(9):1442-1448; > The myeloperoxidase product hypochlorous acid gene... Arterioscler Thromb Vasc Biol. 2013; 33(5):1020-1027; > Myeloperoxidase-derived chlorinating species induc... Antioxid Redox Signal. 2012; 17(8):1043-1052; > Psoriasis alters HDL composition and cholesterol e... J Lipid Res. 2012; 53(8):1618-1624; > Laropiprant Attenuates EP3 and TP Prostanoid Recep... PLoS One. 2012; 7(8):e40222-e40222; > Interaction of eosinophils with endothelial cells ... Eur J Immunol. 2011; 41(8):2379-2389; > Protein carbamylation renders high-density lipopro... Antioxid Redox Signal. 2011; 14(12): 2337-2346.; > Uremia Alters HDL Composition and Function.... J Am Soc Nephrol. 2011; 22(9):1631-1641; > Microwave-assisted high-throughput acid hydrolysis... J Chromatogr A. 2010; 1217(50):7826-7832; > Endothelium-derived prostaglandin I(2) controls th... J Allergy Clin Immunol. 2010; 125(5): 1105-1113.; > The Prostaglandin E2 Receptor EP4 Is Expressed by ... Arterioscler Thromb Vasc Biol. 2010; 30(12): 2416-2423.